**6. References**

Aka, P.; Mateuca, R.; Buchet, J.P.; Thierens, H. & Kirsch-Volders, M. (2004) Are genetic polymorphisms in OGG1, XRCC1 and XRCC3 genes predictive for the DNA strand

The Influence of Individual Genome Sensitivity in DNA Damage Repair

subjects. *Mutat Res* 307: 323-333.

humans. *Mutat Res* 211(1): 13-17.

*Carcinog Mutagen* 21: 431–439.

Kosice and Sofia). *Mutat Res* 620: 145–154.

507–519.

France.

29(2): 67-73. Review.

*Med* 16: 161–165.

Assessment in Chronic Professional Exposure to Low Doses of Ionizing Radiation 455

Berrington, A.; Darby, S.C.; Weiss, H.A. & Doll, R. (2001) 100 years of observation on British

Berwick, M. & Vineis, P. (2000) Markers of DNA repair and susceptibility to cancer in

Boffetta, P.; Caporaso, N.; Cuzick, J.; Lang, M.; Vineis, P.; Malats, N. & D'Errico, A. (1999)

Bolus, N.E. (2001) Basic review of radiation biology and terminology. *J Nucl Med Technol* 46

Bonassi, S.; Ugolini, D.; Kirsch-Volders, M.; Stromberg, U.; Vermeulen, R. & Tucker, J.D.

Bosi, A. & Olivieri, G. (1989) Variability of the adaptive response to ionizing radiations in

Boutcher, S. & Haas, T. (1985) External radiation doses to nuclear medicine technologists

Cardisi, E.; Vrijheid, M.; Blettner, M.; Gilbert, E.; Hakama, M.; Hill, C.; Howe, G.; Kaldor, D.;

Cardoso, R. S.; Takahashi-Hyodo, S.; Peitl Jr, P.; Ghilardi-Neto, T. & Sakamoto-Hojo, E.T.

Carrano, A.V. & Natarajan, A.T. (1988) Considerations for population monitoring using cytogenetic techniques. ICPEMC publication 14. *Mutat Res* 204: 379–406. Cebulska-Wasilewska, A.; Pawłyk, I.; Panek, A.; Wiechec,´ A.; Kalina, I.; Popov, T.;

(2001) Evaluation of chromosomal aberrations, micronuclei, and sister chromatid exchanges in hospital workers chronically exposed to ionizing radiation. *Teratog* 

Georgieva, T. & Farmer, P.B. (2007) Exposure to environmental polycyclic aromatic hydrocarbons: influences on cellularsusceptibility to DNA damage (sampling

literature and future prospectives. *Environ Mol Mutagen* 45: 258–270. Boothman, D.A.; Bouvard, I. & Hughes, E.N. (1989) Identification and characterisation of X-

ray-induced proteins in human cells. *Cancer Res* 49 (11): 2871-2878.

retrospective cohort study in 15 countries. *Br Med J* 331: 77–80.

humans: An epidemiological review. *J Natl Cancer Inst* 91: 874-897. Berwick, M. (2000) Gene-environment interaction in melanoma. *Forum Geneva* 10: 191– 200. Betti, C.; Davini, T.; Gianessi, L.; Loprieno, N. & Barale, R. (1994) Microgel electrophoresis

radiologists: mortality from cancer and other causes 1897–1997. *Br J Radiol* 34 74:

assay (comet test) and SCE analysis in human lymphocytes from 100 normal

Metabolic polymorphisms and susceptibility to cancer. IARC Publications, 44 Lyon,

(2005) Human population studies with cytogenetic biomarkers: review of the

from procedures using 99mTc radiopharmaceuticals. *Can J Radiogr Radiother Nucl* 

Muirhead, C.R.; Schubauer-Berigan, M.; Yoshimura, T.; Bermann, F.; Cowper, G.; Fix, J.; Hacker, C.; Heinmiller, B.; Marshall, M.; Thierry-Chef, I.; Utterback, D.; Ahn, ,Y.O.; Amoros, E.; Ashmore, P.; Auvinen, A.; Bae, J.M.; Bernar Solano, J.; Biau, A.; Combalot, E.; Deboodt, P.; Diez Sacristan, A.; Eklof, M.; Engels, H.; Engholm, G.; Gulis, G.; Habib, R.; Holan, K;, Hyvonen, H.; Kerekes, A.; Kurtinaitis, J.; Malker, H.; Martuzzi, M.; Mastauskas, A.; Monnet, A.; Moser, M.; Pearce, M.S.; Richardson, D.B.; Rodriguez-Artalejo, F.; Rogel, A.; Tardy, H.; Telle-Lamberton, M.; Turai, I.; Usel, M. & Veress, K. (2005) Risk of cancer after low doses of ionising radiation:

break repair phenotype and genotoxicity in workers xx)posed to low dose ionising radiations? *Mutat Res* 556: 169-181.


Andreassen, C.N. (2005) Can risk of radiotherapy-induced normal tissue complications be

Andreassi, M.G.; Foffa, I.; Manfredi, S.; Botto, N.; Cioppa, A. & Picano, E. (2009) Genetic

Angelini, S.; Kumar, R.; Carbone, F.; Maffei, F.; Forti, G.C.; Violante, F.S.; Lodi, V.; Curti, S.;

Ashby, J.; Tinwell, H.; Lefevre, P.A. & Browne, M.A. (1995) The single cell gel

Au, W.W. (1991) Monitoring human populations for effects of radiation and chemical

Au WW (2006) Heritable susceptibility factors for te development of cancer. *J Radiat Res* 47B:

Bailey, S. & Goodwin, E. (2004) DNA and telomeres: beginnings and endings. *Cytogenet* 

Bailey, S.; Cornforth, M.; Ullrich, R. & Goodwin, E. (2004) Dysfunctional mammalian telomeres join with DNA double-strand breaks. *DNA Repair* 3: 349-357. Bajpayee, M.; Dhawan, A.; Parmar, D.; Pandey, A.K.; Mathur, N. & Seth, P.K. (2002) Gender-

Balasem, A,N. & Ali, A.S.K. (1991) Establishment of dose–response relationships between

Barquinero, J.F.; Barrios, L.; Caballin, M.R.; Miro, R.; Ribas, M.; Subias, A. & Egozcue, J.

Barquinero, J.F.; Barrios, L.; Caballin, M.R.; Miro, R.; Ribas, M.; Subias, A. & Egozcue, J.

Barquinero, J.F.; Barrios, L.; Caballin, M.R.; Miro, R.; Ribas, M.; Subias, A. & Egozcue, J.

Berasati Nia, A.; Van Schooten: F.J.; Schilderman, P.A.E.L.; De Kok, T.M.C.M.; Haenen, G.R.;

related differences in basal DNA damage inlymphocytes of a healthy Indian

doses of Cs137 gamma-rays and frequencies of micronuclei in human peripheral

(1993) Cytogenetic analysis of lymphocytes from hospital workers occupationally

(1995) Occupational exposure to radiation induces an adaptive response in human

(1996) Decreased sensitivity to the cytogenetic effects of bleomycin in individuals

Van Herwijnen, M.H.M.; Van Agen, E.; Pachen, D. & Kleinjans, J.C.S. (2001) A multi-biomarker approach to study the effects of smoking on oxidative DNA damage and repair and antioxidative defence mechanisms. *Carcinogenesis* 21: 395–

exposures using cytogenetic techniques. *Occup Med* 4:597-611.

population using the alkaline Comet assay. *Mutat Res* 520: 83-91.

exposed to low levels of ionizing radiation. *Mutat Res* 286: 275–279.

occupationally exposed to ionizing radiation. *Mutat Res* 354:81-86.

predicted from genetic profiles? *Acta Oncologica* 44: 801-815.

radiations? *Mutat Res* 556: 169-181.

*Mutat Res* 666(1-2): 57-63.

*Mutat Res* 570: 105-117.

*Genome Res* 104: 109-115.

13-17

401.

length and moment. *Mutagenesis* 10(2): 85-90.

blood lymphocytes. *Mutat Res* 259:133–138.

lymphocytes. *Int J Radiat Biol* 67 (2): 187-191.

break repair phenotype and genotoxicity in workers xx)posed to low dose ionising

polymorphisms in XRCC1, OGG1, APE1 and XRCC3 DNA repair genes, ionizing radiation exposure and chromosomal DNA damage in interventional cardiologists.

Hemminki, K. & Hrelia, P. (2005) Micronuclei in humans induced by exposure to low level of ionizing radiation: influence of polymorphims in DNA repair genes.

electrophoresis assay for induced DNA damage (comet assay): measurement of tail


The Influence of Individual Genome Sensitivity in DNA Damage Repair

Assessment in Chronic Professional Exposure to Low Doses of Ionizing Radiation 457

Frenzili, G.; Betti, C.; Davini, T.; Desideri, M.; Fornai, E.; Gianessi, L.; Maggiorelli, F.;

Goode E.L-; Ulrich C.M. & Potter J.D. (2002) Polymorphisms in DNA repair genes and associations with cancer risk. *Cancer Epidemiol Biomarkers Prev* 11: 1513–1530. Gourabi, H. & Mozdarani, H. (1998) A cytokinesis-blocked micronucleus study of the

Hall, E.J. & Giaccia, A.J. (2006) Radiobiology for the Radiologist. 6th edn. Lippincott

He, J.L.; Chen, W.L.; Jin, L.F. & Jin, H.Y. (2000) Comparative evaluation of the in vitro

Hellman, B.; Vaghef, H. & Bostrom, B. (1995) The concepts of tail moment and tail inertia in

Hellman, B.; Vaghef, H.; Friis, L. & Edling, C. (1997) Alkaline single cell gel electrophoresis

Hinds, D.A.; Stuve, L.L.; Nilsen, G.B.; Halperin, E.; Eskin, E.; Ballinger, D.G.; Frazer, K.A. &

Hoffmann H. & Speit G. (2005) Assessment of DNA damage in peripheral blood of heavy smokers with the comet assay and the micronucleus test. *Mutat Res* 581:105-14. Hou, S.M.; Falt, S.; Angelini, S.; Yang, K.; Nyberg, F.; Lambert, B. & Hemminki, K. (2002)

Hu, J.J.; Smith, T.R.; Miller, M.S.; Mohrenweiser, H.W.; Golden, A. & Case, L.D. (2001)

Hu, J.J.; Mohrenweiser, H.W.; Bell, D.A.; Leadon, S.A. & Miller, M.S. (2002a) Symposium

Hu, J.J.; Smith, T.R.; Miller, M.S.; Lohman, K. & Case, L.D. (2002b) Genetic regulation of

Hu, Z.; Ma, H.; Chen, F.; Wei, Q. & Shen, H. (2005) XRCC1 polymorphisms and cancer risk:

Hung, R.J.; Hall, J.; Brennan, P. & Boffetta, P. (2005) Genetic polymorphisms in the base

the single cell gel electrophoresis assay. *Mutat Res* 336: 123-131.

smokers by single cell gel electrophoresis. *Mutat Res* 375: 117-123.

chronic doses of radiation. *Mutagenesis* 13(5): 475-480.

Williams & Wilkins, Philadelphia

radiation. *Mutat Res* 469:223–231.

human populations. *Science* 307: 1072-1079.

and lung cancer risk. *Carcinogenesis* 23: 599-603.

ionizing radiation sensitivity. *Carcinogenesis* 22: 917–922.

*Health* 69: 185-192.

*Pharmacol* 185: 64–73.

215.

14:1810–1818.

925-942.

Paoletti, P. & Barale, R. (1997) Evaluation of DNA damage in leukocytes of ex

radioadaptive response of lymphocytes of individuals occupationally exposed to

micronucleus test and comet assay for the detection of genotoxic effects of X-ray

of DNA fragments in biomonitoring for genotoxicity: an introductiory study on healthy human volunteers. *International Archives of Occupational and Environmental* 

Cox, D.R. (2005) Whole genome patterns of common DNA variation in three

The XPD variant alleles are associated with increased aromatic DNA adduct level

Amino acid substitution variants of APE1 and XRCC1 genes associated with

overview: genetic polymorphisms in DNA repair and cancer risk. *Toxicol Appl* 

ionizing radiation sensitivity and breast cancer risk. *Environ Mol Mutagen* 39: 208-

a meta-analysis of 38 case-control studies. *Cancer Epidemiol Biomarkers Prevent*

excision repair pathway and cancer risk: a HuGE review. *Am J Epidemiol* 162(10): 21


Chen, S.; Tang, D.; Xue, K.; Xu, L.; Ma, G.; Hsu, Y. & Cho, S.S. (2002) DNA repair gene

Coates, P.J.; Lorimore, S.A. & Wright, E.G. (2004) Damaging and protective cell signalling in

Collins, A. & Harrington, V. (2002) Repair of oxidative DNA damage: assessing its

Collins, A.R. (2004) The Comet Assay for DNA damage and repair: Principles, applications

Cornetta, T.; Festa, F.; Testa, A. & Cozzi, R. (2006) DNA damage repair and genetic

Daly, A.K.; Steen, V.M.; Fairbrother, K.S. & Idle, J.R. (1996) CYP2D6 multiallelism. *Meth*

DeMeo, M.; Laget, M.; Castegnaro, M. & Dumenil, G. (1991) Genotoxic activity of potassium

Divine, K.K.; Gilliland, F.D.; Crowell, R.E.; Stidley, C.A.; Bocklage, T.J.; Cook, D.L. &

Domingues, I; Panneerselvam, N.; Escalza, P.; Natarajan, A.T. & Cortes, F. (1993) Adaptive

Dusinska, M.; Collins, A.; Kazimirova, A.; Barancokova, M.; Harrington, V.; Volkovova, K.;

Dusinska, M.; Kazimirova, A.; Barancokova, M.; Horska, A.; Burghardtova, K.; Volkovova,

Fachini, A.L.; Mello, S.S.; Sandrin-Garcia, P.; Junta, C.M.; Ghilardi-Netto, T.; Donadi, E.A.;

Fairbairn, D.W.; Olive, P.L.; O´Neill, K.L. (1995) The comet assay: a comprehensive review.

Fenech, M.; Denham, J.; Francis, W. & Morley, A.A. (1990) Micronuclei in cytokinesis

Frankenberg-Schwager, M. (1989) Review of repair kinetics for DNA damage induced in eukaryotic ce,lls in vitro by ionizing radiation. *Radiother Oncol* 14: 307-320.

polimorphisms: assessment of indivisual sensitivity and repair capacity. *Int J* 

Belinsky, S.A. (2001) The XRCC1 399 glutamine allele is a risk factor for

response to radiation damage in human lymphocytes conditioned with hydrogen peroxide as measured by the cytokinesis-block micronucleus technique. *Mutat Res* 

Staruchova, M.; Horska, A.; Wsolova, L.; Kocan, A.; Petrik, J.; Machata, M.; Ratcliffe, B. & Kyrtopoulos, S. (2004a) Genotoxic effects of asbestos in humans.

K.; Staruchova, M.; Wsolova, L. & Collins, A.R. (2004b) Does occupational exposure to mineral fibres cause DNA or chromosome damage? *Mutat Res* 553: 103–110. Erexon, G.L.; Kligerman, A.D.; Bryant, M.F.; Sontag, M.R. & Halperin, E.C. (1991) Induction

of micronuclei by X-radiation in human, mouse and rat peripheral blood

Da Silva, G.A.; Elza, P. & Sakamoto-Hojo, T. (2009) Gene expression profiles in radiation workers occupationally exposed to ionizing radiation. *J Radiat Res* 50: 61–

blocked lymphocytes of cancer patients following fractionated partial-body

the untargeted effects of ionizing radiation. *Mutat Res* 568: 5-20.

contribution to cancer prevention. *Mutagenesis* 17: 489-493.

permanganate in acidic solutions. *Mutat Res* 260: 295-306.

adenocarcinoma of the lung. *Mutat Res* 461: 273-278.

and limitations. *Mol Biotechnol* 26: 249-261.

*Radiation Oncology Biol Phys* 66 (2): 537-545.

*Carcinogenesis* 23: 1321-1325.

*Enzymol* 272: 199–210.

301: 135–141.

71.

*Mutat Res* 553: 91–102.

*Mutat Res* 339: 37-59.

lymphocytes. *Mutat Res* 253: 193–198.

radiotherapy. *Int J Radiat Biol* 57: 373–383.

XRCC1 and XPD polymorphisms and risk of lung cancer in a Chinese population.


The Influence of Individual Genome Sensitivity in DNA Damage Repair

*Cancer Genet Cytogenet* 124: 71–75.

*Clinica Chimica Acta* 347: 15-24.

population. *Mutation Research* 541: 1–8.

European review. *Mutat Res* 288: 47–63.

Zagreb: Faculty of Science, University of Zagreb.

risk estimation? *Mutat Res* 400: 15–24.

22.

567-580.

Assessment in Chronic Professional Exposure to Low Doses of Ionizing Radiation 459

Maluf, S. & Erdtmann, B. (2001a) Genomic instability in Down syndrome and Fanconi

Maluf, S.W.; Passos, D.F.; Bacelar, A.; Speit, G. & Erdtmann, B. (2001b) Assessment of DNA

Maluf, S.W. (2004) Monitoring DNA damage following radiation exposure using

Marcon, F.; Andreoli, C.; Rossi, S.; Verdina, A.; Galati, R. & Crebelli, R. (2003) Assessment of

Matullo, G.; Peluso, M.; Polidoro, S.; Guarrera, S.; Munnia, A.; Krogh, V.; Masala, G.;

in a population-based study. *Cancer Epidemiol. Biomarkers Prev* 12: 674–677 McKelvey-Martin, V.J.; Green, M.H.L.; Schmezer, P.; Pool-Zobel, B.L.; De Me´o, M.P. &

McKelvey-Martin, V.J.; Ho, E.T.S.; McKeown, S.R.; Johnston, S.R.; McCarthy, P.J.; Rajab, N.F.

test and the comet assay. *Environ Mol Mutagen* 38: 311–315

anemia assessed by micronucleus analysis and single-cell gel electrophoresis.

damage in lymphocytes of workers exposed to X-radiation using the micronucleus

cytokinesis-block micronucleus method and alkaline single-cell gel electrophoresis.

individual sensitivity to ionizing radiation and DNA repair efficiency in a healthy

Berrino, F.; Panico, S.; Tumino, R.; Vineis, P. & Palli, D. (2003) Combination of DNA repair gene single nucleotidepolymorphisms and increased levels of DNA adducts

Collins, A. (1993) The single cell gel electrophoresis assay (comet assay): a

& Downes, C.S. (1998) Emerging applications of the single cell gel electrophoresis (Comet) assay. I. Management of invasive transitionalcell human bladder carcinoma. II. Fluorescent in situ hybridization Comets for the identification of damaged and repaired DNA sequences in individual cells. *Mutagenesis* 13: 1–8. Milić, M.; Rozgaj, R.; Kašuba, V.; Kubelka, D.; Angelini, S. & Hrelia, P. (2010) DNA repair genes and radiation sensitivity*. Arh Hig Rada Toksikol* 61 Supplement: 107-121. Milić, M. (2010) Važnost individualne osjetljivosti za procjenu rizika od oštećenja genoma

pri kroničnoj profesionalnoj izloženosti niskim dozama ionizirajućeg zračenja [The significance of individual genome sensitivity in risk assessment of chronic professional exposure to low doses of ionizing radiation; in Croatian]. [PhD thesis].

susceptibility: a paradigm for the promises and perils of individual and population

estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA repair genes. *Mutat Res* 526: 93–125. Monsieurs, M.A.; Thierens, H.M.; Vral, A.M.; Van De Wiele, C.; De Ridder, L.I. & Dierckx,

R.A. (2000) Adaptive response in patients treated with 131I. *J Nucl Med* 41 (1): 17-

radiation-induced genomic instability and bystander effects *in vitro. Radiat Res* 159:

Mohrenweiser, H.W. & Jones, I.M. (1998) Variation in DNA repair is 1 a factor in cancer

Mohrenweiser, H.W.; Wilson, D.M. & Jones, I.M. (2003) Challenges and complexities in

Morgan, W.F. (2003) Non-targeted and delayed effects of exposure to ionizing radiation: i.


Ikushima, T. (1989) Radio-Adaptive Response: Characterization of a cytogenetic repair

Ikushima, T. (1992) Radio-adaptive response: involvement of induction of specific gene

Ikushima, T.; Aritomi, H. & Morisita, J. (1996) Radioadaptive Response: Efficient repair of radiation-induced DNA damage in adapted cells. *Mutat Res* 358(2):193-198. Jeggo, P. & Lavin, M.F. (2009) Cellular radiosensitivity: how much better do we understand

Jha, A.N. & Sharma, T. (1991) Enhanced frequency of chromosome aberrations in workers occupationally exposed to diagnostic X-rays. *Mutat Res* 260: 343–348. Kassie, F.; Parzefall, W. & Knasmuller, S. (2000) Single cell gel electrophoresis assay: new

Kotsopoulos, J.; Chen, Z.; Vallis, K.A.; Poll, A.; Ainsworth, P. & Narod, S.A. (2007) DNA

Kruszewski, M.; Wojewodzka, M.; Iwanenko, T.; Collins, A.R. & Szumiel, I. (1998)

Kubelka, D.; Sviličić, N.; Kralik, I.; Belamarić, N.; Faj, D.; Novosel, N.; Vukić, V. & Tečić Z.

repair capacity as a possible biomarker of breast cancer risk in female BRCA1

Application of the comet assay for monitoring DNA damage in workers exposed to

(2011) .Analiza učinkovitosti i usklanenosti s EU propisima zakonodavstva kojim se regulira radiološka i nuklearna sigurnost [Analysis of efficacy and conformity with the EU acquis communautaire of the radiation protection and nuclear safety legislative; *in Croatian*]. In: Krajcar Bronić I, Kopjar N, Milić M, 1 Branica G, editors. Proceedings of the 8th Symposium of the Croatian Radiation Protection

nucleotide polymorphisms in the XPG gene: determination of role in DNA repair

Etzel, C. & Bondy, M.L. (2009) Association and interactions between DNA repair gene polymorphisms and adult glioma. *Cancer Epidemiol Biomarkers Prev* 18(1): 204-

D.A. (2000) XPD polymorphisms: effects on DNA repair proficiency. *Carcinogenesis* 

incidence of haematological cancer among physicians in a University Hospital. *Int*

Kumaravel, T.S. & Jha, A.N. (2006) Reliable Comet assay measurements for detecting DNA damage induced by ionising radiation and chemicals. *Mutat Res* 605: 7-16.

Liu, Y.; Scheurer, M.E.; El-Zein, R.; Cao, Y.; Do, K.A.; Gilbert, M.; Aldape, K.D.; Wei, Q.;

Lunn, R.M.; Helzlsouer, K.J.; Parshad, R.; Umbach, M.D.; Harris, E.L.; Sanford, K.K. & Bell

Maitre, A.; Colonna, M.; Gressin, C.; Menegoz, F. & de Gaudemaris, R. (2003) Increased

technique for human biomonitoring studies. *Mutat Res* 463: 13–31.

chronic low-dose irradiation: II. Base damage. *Mutat Res* 416: 37–57.

Association; 13-15 Apr 2011; Krk, Croatia. Zagreb: Denona; p. 31-37. Kumar, R.; Hoglund, L.; Zhao, Ch.; Forsti, A.; Snellman, E. & Hemminki, K. (2003) Single

*Res* 227 (4): 241-246.

Publishers BV, Amsterdam, 255–263.

mutation carriers. *Br J Cancer* 96:118–125.

and breast cancer risk. *Int J Cancer* 103: 671-675.

*Arch Occup Environ Health* 76: 24–28.

214

21: 551–555.

Little, J.B. (2000) Radiation carcinogenesis. *Carcinogenesis* 21: 397–404.

it? *Int J Radiat Biol* 85:1061-1081.

induced by low-level ionizing radiation in cultured Chinese hamster cells. *Mutat* 

expression by low doses of ionizing radiation. In: Sugahara T, Sagan L, Aoyama T(ed.) Low Dose Irradiation and Biological Defence Mechanisms. Elsevier Science


The Influence of Individual Genome Sensitivity in DNA Damage Repair

doses of irradiation. *Int J Radiat Biol* 76: 1493-1500.

lymphocytes *in vitro. Radiat Res* 164: 132–140.

*Environ Mol Mutagen* 30(2): 153-160.

61-71.

*Cancer* 95: 86–91.

211: 7–12.

504: 101-118.

508-511.

S9–S12.

22.

191.

Assessment in Chronic Professional Exposure to Low Doses of Ionizing Radiation 461

Plappert, U.G.; Stocker, B.; Fender, H. & Fliedner, T.M. (1997) Changes in the repair capacity

Price, A. (1993) The repair of ionising radiation- induced damage to DNA. *Cancer Biology* 4:

Rajaee-Behbahani, N.; Schmezer, P.; Risch, A.; Rittgen, W; Kayser, K.W.; Dienemann, H.;

Robson, T., Joiner, M.C.; Wilson, G.D.; McCullough, W.; Price, M.E.; Logan, I.; Jones, H.;

with a potential role in induced radioresistance. *Radiat Res* 152 (5): 451-461. Roos, W.P.; Binder, A. & Bohm, L. (2000) Determination of the initial DNA damage and

Rzeszowska-Wolny, J.; Polanska, J.; Pietrowska, M.; Palyvoda, O.; Jaworska, J.; Butkiewicz,

Sankaranarayanan, K.; Duyn, A.; Loos, M.J. & Natarajan, A.T. (1989) Adaptive response of

Sari-Minodier, I.; Orsiere, T.; Auquier, P.; Martin, F. & Botta, A. (2007) Cytogenetic

Sasaki, M.S.; Ejima, Y.; Tachibana, A.; Yamada, T.; Ishizaki, K.; Shimizu, T. & Nomura, T.

Setlow, R.B. (1983) Variations in DNA repair among humans. In: Harris CC, Autrup HN

Seymour, C.B. & Mothersill, C. (2000) Relative contribution of bystander and targeted cell

Shadley, J.D. & Wiencke, J.K. (1989) Induction of the adaptive response by x-rays is

Shadley, J.D. (1994) Chromosomal adaptive response in human lymphocytes. *Radiat Res* 138:

Shadley, J.D. & Wolff, S. (1987) Very low doses of X-rays can cause human lymphocytes to

Shastry, B.S. (2009) SNPs: impact on gene function and phenotype. *Methods Mol Biol* 578: 3-

Singh, N.P.; McCoy, M.T.; Tice, R.R. & Schneider, L.L. (1988) A simple technique for

quantitation of low levels of DNA damage in individual cells. *Exp Cell Res* 175:184-

become less susceptible to ionizing radiation. *Mutagenesis* 2: 95–96.

(ed.) Human Carcinogenesis. New York: Academic Press: 231-254.

dependent on radiation intensity. *Int J Radiat Biol* 56: 107-118.

low doses of ionizing radiation. *Mutat Res* 629(2): 111-121.

of blood cells as a biomarker for chronic low-dose exposure to ionizing radiation.

Schulz, V.; Drings, P., Thiel, S. & Bartsch, H. (2001) Altered DNA repair capacity and bleomycin sensitivity as risk markers for non-small cell lung cancer. *Int J* 

McKeown, S.R. & Hirst, D.G. (1999) A novel human stress response-related gene

residual DNA damage remaining after 12 hours of repair in eleven cell lines at low

D. & Hancock, R. (2005) Influence of polymorphisms in DNA repair genes XPD, XRCC1 and MGMT on DNA damage induced by gamma radiation and its repair in

human lymphocytes to low-level radiation from radioisotopes or X-rays. *Mutat Res* 

monitoring by use of the micronucleus assay among hospital workers exposed to

(2002) DNA damage response pathway in radioadaptive response. *Mutat Res* 33

killing to the low-dose region of the radiation dose-response curve. *Radiat Res* 153:


Mothersill, C.; Kadhim, M.A.; O' Reilly, S.; Paphworth, D.; Mardsen, S.J.; Seaymoure, C.B. &

Mothersill, C.; Rea, D.; Wright, E.G.; Lorimore, S.A.; Murphy, D.; Seymour, C.B. & O'Malley,

Muller, W.U.; Bauch, T.; Stuben, G.; Sack, H. & Streffer, C. (2001) Radiation sensitivity of

Muller, W.U.; Bauch, T.; Streffer, C. & von Mallek, D. (2002) Does radiotherapy affect the

Naccarati, A.; Soucek, P.; Stetina, R.; Haufroid, V.; Kumar, R.; Vodickova, L.; Trtkova, K.;

Norppa, H. (2004) Cytogenetic biomarkers and genetic polymorphisms. *Toxicol Lett* 149:

Nowak, B. & Jankowski, J. (1991) Occupational exposure in operational radiology. *Pol J* 

Okayasu, R.; Suetomi, K.; Yu, Y.; Silver, A.; Bedford, J.; Cox, R. & Ullrich, R. (2000) A

Olive, P.L.; Banath, J.P. & Durand, R.E. (1990) Heterogeneity in radiation-induced DNA

Olive, P.L. (1999) DNA damage and repair in individual cells: aplications of the comet assay in radiobiology. *International Journal of Radiation Biology* 75(4): 395-405. Olivieri, G.; Bodycote, J. & Wolff, S. (1984) Adaptive response of human lymphocytes to low

Olivieri, G. & Bosi, A. (1990) Possible causes of variability of the adaptive response in

Padovani, L.; Appolloni, M.; Anzidei, P.; Tedeschi, B.; Caporossi, D.; Vernole, P. & Mauro, F.

Parl, F.F. (2005) Glutathione S-transferase genotypes and cancer 1 risk. *Cancer Lett* 221:123–

Plappert, U.; Raddatz, K.; Roth, S. & Fliedner, T.M. (1995) DNA damage detection in man

concentrations of radioactive thymidine. *Science* 223: 594–597.

Basic and Applied Aspects. Springer-Verlag, Berlin, 130–140.

keratinocyte cell line. *Int Radiat Biol* 76 (6): 799-806.

comet assay. *Radiat Environ Biophys* 40: 83–89.

damage. *Mutat Res* 593: 22–31

*Occup Med Environ Health* 4: 169–174.

monitoring. *Stem Cells* 13(1): 215-222.

mouse. *Cancer Res*. 60: 4342-4345.

*Research* 122: 86-94.

(1-2): 33-38.

129.

outcome of the comet assay? *Br J Radiol* 75: 608–614.

1465-1471.

309–334.

Wright, E.G. (2000) Dose- and time-response relationships for lethal mutations and chromosomal instability induced by ionizing radiation in an immortalized human

K. (2001) Individual variation in the production of a bystander signal following irradiation of primary cultures of normal human urothelium. *Carcinogenesis* 22 (9):

lymphocytes from healthy individuals and cancer patients as measured by the

Dusinska, M.; Hemminki, K. & Vodicka, P. (2006) Genetic polymorphisms and possible gene-gene interactions in metabolic andDNA repair genes: Effects on DNA

deficiency in DNA repair and DNA-PKcs expression in the radiosensitive BALB/c

damage and repair in tumor and normal cells using the "comet" assay. *Radiation* 

human lymphocytes. In: Obe G, Natarajan A T(ed.) Chromosomal Aberrations,

(1995) Do human lymphocytes exposed to the fallout of the Chernobyl accident exhibit an adaptive response? I. Challenge with Ionizing Radiation. *Mutat Res* 332

after radiation exposure-the comet assay- its possible application for human


The Influence of Individual Genome Sensitivity in DNA Damage Repair

1995, *Health Phys* 82: 455–466.

*Mol Carcinog* 42: 127–141.

lymphocytes. *Mutagenesis* 11: 291–297.

763.

186.

380.

5616.

London, 439-445.

Berlin, 140–149.

agents. *Mutat Res* 358: 135–142.

*Carcinogenesis* 25: 1689-1694

1993. *J Epidemiol* 9: 61–72.

Assessment in Chronic Professional Exposure to Low Doses of Ionizing Radiation 463

Wang, J.X.; Zhang, L.A.; Li, B.X.; Zhao, Y.C.; Wang, Z.Q.; Zhang, J.Y. & Aoyama, T. (2002)

Wang, Z.Q.; Saigusa, S. & Sasaki, M.S. (1991) Adaptive response to chromosome damage in

Weiss, J.M.; Goode, E.L.; Ladiges, W.C. & Ulrich, C.M. (2005) Polymorphic variation in

Wiencke, J.K.; Afzal, V; Olivieri, G. & Wolff, S. (1986) Evidence that the (3h) thymidine

Winsey, S.L.; Haldar, N.A.; Marsh, H.P.; Bunce, M.; Marshall, S.E.; Harris, A.L.;

Wojcik, A.; Sauer, K.; Zolzer, F.; Bauch, T. & Muller, W.U. (1996) Analyses of DNA damage

Wojewodzka, M.; Kruszewski, M.; Iwanenko, T.; Collins, A.R. & Szumiel, I. (1998)

Wolff, S.; Oliviery, G. & Afzal, V. (1990) Adaptation of human lymphocytes to radiation or

Wolff, S. (1992) Low-dose exposures and the induction of adaptation. In: Sugahara, T.,

Wolff, S. (1996) Aspects of the adaptive response to very low doses of radiation and other

Yamane, A.; Kohno, T.; Ito, K.; Sunaga, N.; Aoki, K.; Yoshimura, K.; Murakami, H.; Nojima,

Yoshinaga, S.; Aoyama, T.; Yoshimoto, Y. & Sugahara, T. (1999) Cancer mortality among

Mechanisms. Elsevier Science Publishers BV, Amsterdam, 21–28.

chronic low-dose irradiation: I. Strand breakage. *Mutat Res* 416:21–35. Wolff, S.; Wiencke, J.K. & Afzal, V. (1989) Biological Bases of Risk Assessment. In:

chromosomal aberrations and single-strand breaks in DNA. *Carcinogenesis* 25: 757–

Cancer incidence and risk estimation among medical X-ray workers in China, 1950–

cultured human lymphocytes primed with low doses of X-rays. *Mutat Res* 246: 179–

hOGG1 and risk of cancer: a review of the functional and epidemiologic literature.

induced adaptive response of human lymphocytes to subsequent doses of x-rays involves the induction of a chromosomal repair mechanism. *Mutagenesis* 1(5): 375-

Wojnarowska, F. & Welsh, K.I. (2000) A variant within theDNA repair gene XRCC3 is associated with the development of melanoma skin cancer. *Cancer Res* 60: 5612-

recovery processes in the adaptive response to ionising radiation in human

Application of the comet assay for monitoring DNA damage inworkers exposed to

Baverstock KF and Stather JW (ed.) Low Dose Radiation. Taylor and Francis,

chemical mutagens: differences in cytogenetic repair. In: Obe G., Natarajan, A.T. (ed.) Chromosomal Aberrations, Basic and Applied Aspects. Springer-Verlag,

Sagan, L.A., Aoyama, T. (ed.) Low Dose Irradiation and Biological Defence

Y. & Yokota, J. (2004) Differential ability of polymorphic OGG1 proteins to suppress mutagenesis induced by 8-hydroxyguanine in human cell in vivo.

radiological technologists in Japan: updated analysis of follow-up data from 1969 to


Singh, N.P. (2000) Microgels for estimation of DNA strand breaks, DNA protein crosslinks

Stecca, C. & Gerber, G.B. (1998) adaptive response to dna-damaging agents: a review of

Sturgis, E.M.; Castillo, E.J.; Li, L.; Zheng, R.; Eicher, S.A.; Clayman, G.L.; Strom, S.S.; Spitz,

Szumiel, I. (1998) Monitoring and signaling of radiation-induced damage in mammalian

Tedeschi, B.; Caporossi, D.; Vernole, P.; Padovani, L.; Appolloni, M.; Anzidei, P. & Mauro, F.

Tedeschi, B.; Caporossi, D.; Vernole, P.; Padovani, L. & Mauro, F. (1996) Do human

Tice, R.R.;Andrews, P.W.; Hirai, O. & Singh, N.P. (1990) The single cell gel (SCG) assay: an

Tice, R.R. (1995) The single cell gel/comet assay: a microgel electrophoretic technique for the

Touil, N.; Aka, P.V.; Buchet, J.P.; Thierens, H. & Kirsch-Volders, M. (2002) Assessment of

Trzeciak, A.R.; Barnes, J.; Ejiogu, N.; Foster, K.; Brant, L.J.; Zonderman, A.B. & Evans, M.K.

United Nations Scientific Committee on the Effects of Atomic Radiation, Sources and effects

Valverde, M.; Ostrosky-Wegman, P.; Rojas, E.; Fortoul, T.; Meneses, F.; Ramírez, M.; Díaz-

M.R. & Wei, Q. (1999) Polymorphisms of DNA repair gene XRCC1 in squamous

(1995) Do Human lymphocytes exposed to the fallout of the Chernobyl accident exhibit an adaptive response? II. Challenge with bleomycin. *Mutat Res* 332 (1-2):

lymphocytes exposed to the fallout of the chernobyl accident exhibit an adaptive response? III. Challenge with bleomycin in lymphocytes from children hit by the

electrophoretic technique for the detection of DN damage in individual cells. In: Witmer, C.M., Snyder, R.R., Hollow, D.J., Kalf, G.F., Kocsis, J.J., Sipes, J.G. (ed.) Biological reactive intermediates, IV Molecular and cellular effects and their impact

detection of DNA damage and repair in individual cells. In: Phillis DH, Venitt S

genotoxic effects related to chronic low level exposureto ionizing radiation using

(2008) Age, sex, and race influence single-strand break repair capacity in a human

of ionizing radiation UNSCEAR 2000 report, vol. 1, http://www.unscear.org. UNSCEAR (United Nations Scientific Committee on theEffects of Atomic Radiation), 2000. Sources and effects of ionizing radiation. Report to the General

Barriga, F. & Cebrian, M. The application of single cell gel electrophoresis or Comet assay to human monitoring studies. *Salud Publica Mex.* 1999;41 Suppl 2:S109-13. Vodicka, P.; Kumar, R.; Stetina, R.; Sanyal, S.; Soucek, P.; Haufroid, V.; Dusinska, M.;

Kuricova, M.; Zamecnikova, M., Musak, L.; Buchancova, J.; Norppa, H.; Hirvonen, A.; Vodickova, L.; Naccarati, A.; Matousu, Z. & Hemminki, K. (2004) Genetic polymorphismsin DNA repair genes and possible links with DNA repair rates,

potential mechanisms. *Biochem Pharmacol* 55 (7): 941-951.

cell carcinoma of the head and neck. *Carcinogenesis* 20: 2125-2129.

initial acute dose of ionizing radiation. *Mutat Res* 354 (1): 77-80.

(ed.) *Environmental Mutagenesis*. Bioscientific, Oxford, 315-339.

biomarkers for DNA damage and repair. *Mutagenesis* 17: 223–232.

on human health. New York, Plenum Press, 157-164.

population. *Free Radic Biol Med* 45:1631-1641.

and apoptosis. *Mutat Res* 455: 111-127.

cells. *Radiat Res* 150: 92-101.

299-300.

Assembly.

chromosomal aberrations and single-strand breaks in DNA. *Carcinogenesis* 25: 757– 763.


**20** 

*Taiwan* 

**Application of Host Cell Reactivation in** 

Yi-Shan Tsai1, Jau-Ling Huang2 and Chang-Shen Lin3

*1Center of Excellence for Environmental Medicine,* 

*Kaohsiung Medical University, Kaohsiung 2Department of Bioscience Technology, Chang Jung Christian University, Tainan* 

*Kaohsiung Medical University, Kaohsiung* 

*3Graduate Institute of Medicine,* 

**Evaluating the Effects of Anticancer Drugs** 

**DNA Repair Activity in Head and Neck Cancer** 

DNA repair pathways are targets of numerous anticancer drugs including natural and chemical compounds, which direct cancer cells toward apoptosis. However, different types of cancer cells consist of various alterations in DNA repair genes that make cancer cells become drug-resistant and lead to treatment failure and disease recurrence. On the contrary, cancer cells may also possess defects in certain DNA repair pathway that make them are susceptible to certain compounds, which inhibit another DNA repair pathway inside the cancer cells. As a result, these compounds selectively kill the cancer cells and are less harmful to the normal ones. Understanding the effects of anticancer drugs on DNA repair as well as the DNA repair activity of cancer cells themselves are important for improvement of anticancer treatment. Similarly, this information is helpful for elucidation of the carcinogenicity of environmental toxicants. This chapter introduces the crosstalk between anticancer drugs, environmental toxicants and DNA repair pathways in head and neck cancer. In addition, the application of an easy, fast and measurable *in vivo* functional assay for nucleotide excision repair (NER) and DNA repair via homologous recombination (HR) and non-homologous end-joining (NHEJ) pathways is shown to examine the cellular DNA repair activity responding to anticancer drugs or environmental toxicants. By which the functional roles of DNA repair genes in response to anticancer treatments and genotoxic

**2. Roles of DNA repair genes/pathways in cancer development and treatment**  DNA repair genes play a pivotal role in the maintenance of genome integrity. Defects or dysregulation of DNA repair genes can result in genomic instability (GIN), which is a common feature of cancer cells (Hanahan & Weinberg, 2000). To prevent this, human cells evolve several

substances could be evolved in head and neck cancer cells.

**1. Introduction** 

 **and Environmental Toxicants on Cellular** 

Youngblom, J.H.; Wiencke, J.K. & Wolff, S. (1989) Inhibition of the adaptive response of human lymphocytes to very low doses of ionizing radiation by the protein synthesis inhibitor cycloheximide. *Mutat Res* 227(4):257-261.
