The Toxification Effects of Aflatoxin B1

*Aflatoxin B1 Occurrence, Detection and Toxicological Effects*

Klaikaew N, Tangkijvanich P, et al. Prevalence of aflatoxin induced p53 mutation at codon 249 (R249s) in hepatocellular carcinoma patients with and without hepatitis B surface antigen (HBsAg). Asian Pacific Journal of Cancer Prevention. 2013;**14**:7675-7679.

DOI: PMID24460352

kfj039

[34] Gursoy-Yuzugullu O,

Yuzugullu H, Yilmaz M, Ozturk M. Aflatoxin genotoxicity is associated with a defective DNA damage response

bypassing p53 activation. Liver International. 2011;**31**:561-571. DOI: 10.1111/j.1478-3231.2011.02474.x

[35] Van Vleet TR, Watterson TL, Klein PJ, Coulombe RA Jr. Aflatoxin B1 alters the expression of p53 in cytochrome P450-expressing human lung cells. Toxicological Sciences. 2006;**89**:399-407. DOI: 10.1093/toxsci/

[36] Chan KT, Hsieh DP, Lung ML. In vitro aflatoxin B1-induced p53

Taketomi A, Taguchi K, Yoshizumi T, Uchiyama H, et al. Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern Japan. Liver International. 2011;**31**:1366-1372. DOI: 10.1111/j.1478-3231.2011.02572.x

[37] Shirabe K, Toshima T,

[38] Long XD, Yao JG, Zeng Z,

10.5772/20792

Huang CH, Huang ZS, Huang YZ, et al. DNA repair capacity-related to genetic polymorphisms of DNA repair genes and aflatoxin B1-related hepatocellular carcinoma among Chinese population. In: Kruman I, editor. DNA Repair. Rijeka: InTech; 2011. pp. 505-524. DOI:

mutations. Cancer Letters. 2003;**199**:1-7. DOI: 10.1016/S0304-3835(03)00337-9

Ecotoxicology and Environmental Safety. 2019;**176**:137-145. DOI: 10.1016/j.

[27] Engin AB, Engin A. DNA damage checkpoint response to aflatoxin B1. Environmental Toxicology and Pharmacology. 2019;**65**:90-96. DOI:

[28] Coskun E, Jaruga P, Vartanian V, Erdem O, Egner PA, Groopman JD, et al. Aflatoxin-guanine DNA adducts and oxidatively induced DNA damage in aflatoxin-treated mice in vivo as measured by liquid chromatographytandem mass spectrometry with isotope dilution. Chemical Research in Toxicology. 2019;**32**:80-89. DOI: 10.1021/acs.chemrestox.8b00202

[29] Liang TJ. p53 proteins and aflatoxin B1: The good, the bad, and the ugly. Hepatology. 1995;**22**:1330-1332. PMID:

[30] Poapolathep S, Imsilp K, Machii K, Kumagai S, Poapolathep A. The effects of curcumin on aflatoxin B1-induced toxicity in rats. Biocontrol Science. 2015;**20**:171-177. DOI: 10.4265/

[31] Bayram S, Rencuzogullari E, Almas AM, Genc A. Effect of p53 Arg72Pro polymorphism on the induction

[32] Qi LN, Bai T, Chen ZS, Wu FX, Chen YY, De Xiang B, et al. The p53 mutation spectrum in hepatocellular carcinoma from Guangxi, China : Role of chronic hepatitis B virus infection and aflatoxin B1 exposure. Liver International. 2015;**35**:999-1009. DOI:

[33] Chittmittrapap S, Chieochansin T, Chaiteerakij R, Treeprasertsuk S,

of micronucleus by aflatoxin B1 in in vitro in human blood lymphocytes. Drug and Chemical Toxicology. 2016;**39**:331-337. DOI: 10.3109/01480545.2015.1121275

7557889

bio.20.171

ecoenv.2019.03.089

10.1016/j.etap.2018.12.006

**116**

10.1111/liv.12460

**119**

**Chapter 7**

An Update

*Yuhua Shan*

**Abstract**

detoxification

chronic way.

**2. Toxic effects of AFB1**

**1. Introduction**

The Toxic Effects of Aflatoxin B1:

Aflatoxin B1 (AFB1) is the most toxic in aflatoxin family. It is well known for its involvement in hepatic carcinogenesis. Other adverse effects include immune weakness, reproduction deficiency, malnutrition, and growth impairment. The key mechanism of AFB1 carcinogenesis is supposed to be epoxidation, which produce the AFB1-8,9-epoxide (AFBO) strongly adductive to DNA molecules. Other metabolites like AFM1, AFH1, and AFL, which retain DNA adductive capability, extend its toxicity. Scientists now found that AFB1 also affected epigenetic regulation, which might shed new light into AFB1 toxicity mechanism researches. The detoxification of AFB1 has always been a hot spot in AFB1-related studies. The major methods can be categorized into physical treatment, biological treatment, chemical treatment, combination strategy, and sorbent additives. None of the methods is 100% perfect, however considering economic factors, simplicity, effectiveness, safety, and preservation of the food nutrition. This review will discuss the toxicity and toxic mechanisms of AFB1. Also, detoxification of AFB1 will be reviewed.

**Keywords:** AFB1, carcinogenesis, DNA adductive capability, epigenetic mutation,

Aflatoxins are fungal metabolites majorly produced by *Aspergillus flavus* and *A. parasiticus* [1]. They are recognized as a family of toxic contaminants in a variety of crops, especially promoted by hot and humid climates as well as improper harvesting and storage process [2]. Among these toxins, aflatoxin B1 (AFB1) is the most hazardous, widely known for its "acute intoxication" targeting the liver featured by acute liver failure and death at a short yet high dosage exposure. Other major adverse effects include carcinogenicity and immunosuppression capacity in a

AFB1 is well known to be hepatotoxic, causing degeneration and necrosis of the liver as well as proliferation of the bile duct and infiltration of inflammatory cells in many species. In recent studies, AFB1 is reported to lead to apoptosis of hepatocytes via an extrinsic mechanism because of high expression of death receptor pathway [3]. Moreover, in 2002, AFB1 has been classified into Group 1 of carcinogens, considering its direct contribution to hepatocellular carcinoma (HCC) [4]. In fact, as early
