**7. Acknowledgments**

This work was supported by CONACyT Mexico (60463) to AA and CONACyT (104316) to BM.

#### **8. References**


occurrence of cancer and other diseases associated with PAH exposure has increased in recent decades. As we discussed in this chapter, the major mechanisms of carcinogenesis induced by these compounds are the interaction of PAHs with DNA to form adducts and the generation of reactive oxygen species. Both activities result in DNA damage and mutagenesis in important sites of the genome. Maintenance of genome integrity is critically dependent on efficient repair of DNA lesions by specific DNA repair mechanisms. In addition, the metabolism of PAHs is related with the ability of cells to prevent damage. Polymorphisms in DNA repair or xenobiotic metabolism-related genes are therefore associated with PAH-induced carcinogenesis. For this reason, understanding the metabolic pathways, biochemical transformations and interactions of PAHs with DNA will help to develop better strategies for risk analysis in exposed individuals. Some studies have shown that several natural compounds could help to reduce DNA damage caused by PAH

These findings offer the possibility for the development of novel drugs that help in the treatment of diseases related to PAH exposure. The analysis of specific polymorphisms of DNA repair genes will help to determine susceptibility in defined populations and the development of new biomarkers and diagnostic tools. Moreover, the study of DNA damage induced by these compounds has included other environmentally important species, such as fish, shrimp and worms. These studies are important in the development of biomarkers for

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**7** 

**Fact and Theory** 

*Sidi Thabet Technopark, Sidi Thabet,* 

Haïtham Sghaier

*Tunisia* 

**DNA Repair: Lessons from the Evolution of** 

**Ionizing-Radiation-Resistant Prokaryotes –** 

*Research Unit UR04CNSTN01 "Medical and Agricultural Applications of Nuclear Techniques", National Center for Nuclear Sciences and Technology (CNSTN),* 

At the outset, I believe that the concept of ionizing-radiation (IR) resistance needs to be clarified in a tangible manner for readers of this chapter. I propose the following general definition adopted in a previous paper (Sghaier et al., 2008): An ionizing-radiation-resistant prokaryotes (IRRP) is any vegetative prokaryote that can thrive after exposure to high, acute IR (generally, with a D10 value - the dose necessary to effect a 90% reduction in Colony Forming Units - greater than 1 kGy) using efficient physiological, genetic and proteic protection and repair mechanisms to fully amend its DNA DSBs. IR resistance has been observed in a broad range of prokaryotic groups (Kopylov et al., 1993), including hyperthermophilic Archaea (*P. abyssi*, *P. furiosus*, *Thermococcus marinus*, *Thermococcus radiotolerans* and *Thermococcus gammatolerans*) (DiRuggiero et al., 1997; Jolivet et al., 2003a; Jolivet et al., 2003b; Jolivet et al., 2004), halophilic Archaea (*Halobacterium* sp.) (Kottemann et al., 2005), the *Deinococcus*-*Thermus* group (many *Deinococcus* sp. and *Truepera radiovictrix*) (Albuquerque et al., 2005), Actinobacteria (*Rubrobacter radiotolerans*, *Rubrobacter xylanophilus* and *Kineococcus radiotolerans*) (Yoshinaka et al., 1973; Ferreira et al., 1999; Phillips et al., 2002; Chen et al., 2004), Proteobacteria (*Methylobacterium radiotolerans* and *Acinetobacter radioresistens*) (Ito and Iizuka, 1971; Nishimura et al., 1994), Cyanobacteria (*Chroococcidiopsis* sp.) (Billi et al., 2000), and Sphingobacteria (*Hymenobacter actinosclerus*) (Collins et al., 2000). However, with the exception of *Deinococcus* and *Pyrococcus*, very little information is available regarding the mechanisms of IR resistance and comparative genomics in the above-mentioned prokaryotes. *D. radiodurans* is the current gold-medallist of IR resistance among prokaryotes with a completely sequenced genome (Liolios et al., 2006; Liolios et al., 2010), and can amend more than 100 DSBs per chromosome, induced by IR, without loss of viability (Moseley, 1983; White et al., 1999). After breaking of its 3.2 Mb genome into 20−30 kb pieces by a high dose of IR, *D. radiodurans* fascinatingly reassembles its genome such that 3 hr later fully restructured nonrearranged chromosomes are present (Galhardo and Rosenberg, 2009). Nine interrelated explanations for the extreme IR resistance of *D. radiodurans* have been proposed: (i) the binding of IrrI (DR0171) to genomic repeat sequences that might prevent exhaustive chromosomal degradation after IR exposure - *irr* for IR resistance - (Udupa et al., 1994), (ii) the

**1. Introduction** 

polymorphisms in DNA repair genes and possible links with DNA repair rates, chromosomal aberrations and single-strand breaks in DNA. *Carcinogenesis*, Vol. 25, No.5, (May), pp. 757-763, 0143-3334 (Print) 0143-3334 (Linking)

