title: Effect of p53 Arg72Pro polymorphism on the induction of micronucleus by aflatoxin B1 in in vitro in human blood lymphocytes.
abstract: Aflatoxin B1 (AFB1) is a class 1 carcinogen produced by Aspergillus flavus and Aspergillus parasiticus that can contaminate a variety of food substances, the liver being its target organ. A common p53 Arg72Pro polymorphism resulting in the substitution of an arginine amino acid by proline amino acid in the transactivating domain has been demonstrated to affect p53 function. The aim of this study is to investigate association between p53 Arg72Pro polymorphism and the frequencies of spontaneous and AFB1-induced DNA damage in peripheral blood lymphocytes from 100 healthy individuals in Turkish population. In vitro cytokinesis-blocked micronucleus (CBMN) assay was used to detect the spontaneous and AFB1-induced DNA damage whereas, genotyping of p53 Arg72Pro polymorphism was carried out by using a polymerase chain reaction restriction fragment length polymorphism assay. During 68 h incubation time, lymphocytes treated with AFB1 (1.56 μg/mL) and S9 mix for a total of 3 h (48-51 h). Treatment of the lymphocytes with AFB1 significantly increased the overall frequencies of micronucleus (MN) when compared to untreated cultures (1.23 ± 0.05 versus 0.55 ± 0.02; p <0.001). Moreover, genotype analysis revealed a statistically significant association between Pro/Pro genotype of p53 Arg72Pro polymorphism and increased frequencies of MN both spontaneous and AFB1-induced cultures when compared Arg/Arg genotype (0.69 ± 0.19 versus 0.46 ± 0.13, p < 0.001; 1.59 ± 0.65 versus 1.01 ± 0.41 p < 0.001; respectively). Our data indicate that p53 Arg72Pro polymorphism plays a significant role in human sensitivity to the genotoxic effects of AFB1. Further investigations in larger sample size and with different ethnic origins as well as including more functional single nucleotide polymorphisms might lead to the identification of novel genetic factors responsible for susceptibility to human carcinogens such as AFB1.
authors.affiliation: a Department of Nursing , Adıyaman School of Health, Adıyaman University , Adıyaman , Turkey .
authors.forename: Süleyman
authors.initials: S
authors.lastname: Bayram
authors.affiliation: b Department of Biology , Faculty of Science and Letters, Adıyaman University , Adıyaman , Turkey .
authors.forename: Eyyüp
authors.initials: E
authors.lastname: Rencüzoğulları
authors.affiliation: c Department of Biology , Institute of Science, Adıyaman University , Adıyaman , Turkey , and.
authors.forename: Abdullah Muttalip
authors.initials: AM
authors.lastname: Almas
authors.affiliation: d Vocational School of Health Services, Adıyaman Univesity , Adıyaman , Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Genç
mesh_terms: D000293:Adolescent; D000328:Adult; D016604:Aflatoxin B1 / Q000633:toxicity*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D009153:Mutagens / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D009153:Mutagens; D016159:Tumor Suppressor Protein p53; D016604:Aflatoxin B1
keywords: Aflatoxin B1; genetic susceptibility; lymphocytes; micronucleus; p53; p53 Arg72Pro polymorphism