CYP1A1 Gene Polymorphisms: Modulator of Genetic Damage in Coal-Tar Workers

Abstract

Aim: It is well known that polycyclic aromatic hydrocarbons (PAHs) such as benzo (a) pyrene have carcinogenic properties and may cause many types of cancers in human populations. Genetic susceptibility might be due to variation in genes encoding for carcinogen metabolizing enzymes, such as cytochrome P-450 (CYP450). Our study aimed to investigate the effect of genetic polymorphisms of CYP1A1 (m1 and m2) on genetic damage in 115 coaltar workers exposed to PAHs at their work place. Methods: Genetic polymorphisms of CYP1A1 were determined by the PCR-RFLP method. Comet and buccal micronucleus assays were used to evaluate genetic damage among 115 coal tar workers and 105 control subjects. Results: Both CYP1A1 m1 and CYP1A1 m2 heterozygous and homozygous (wt/mt+mt/mt) variants individually as well as synergistically showed significant association (P<0.05) with genetic damage as measured by tail moment (TM) and buccal micronuclei (BMN) frequencies in control and exposed subjects. Conclusion: In our study we found significant association of CYP1A1 m1 and m2 heterozygous (wt/mt)+homozygous (mt/mt) variants with genetic damage suggesting that these polymorphisms may modulate the effects of PAH exposure in occupational settings.

Impact of AhR, CYP1A1 and GSTM1 Genetic Polymorphisms on TP53 R273G Mutations in Individuals Exposed to Polycyclic Aromatic Hydrocarbons

“…The polymorphism of CYP1A1(BseMI) of TgC transition is located downstream of exon7 (m2 polymorphism). This polymorphism results in a substitution of a isoleucine (Ile) for a valine (val) mutation at amino acid residue 462 in the heme binding region of CYP1A1 protein (Chen et al, 2006;Giri et al, 2012). GST is a multigene family which includes five subgroups (i.e., α, π, μ,τ and ζ).…”

“…Generally, GSTM1 can detoxify reactive metabolites of benzo(a)pyrene and other PAHs (Smart and Daly, 2000;Chen et al, 2006;Giri et al, 2012). Here, we found that the frequency of variants in the AhR Lys 554 and CYP1A1 val variant genotype and GSTM1 null genotype showed slight higher in exposed group (63.7%, 62.8%, 58.4%, respectively) than in control subjects (59.8%, 61.0%, 57.3%, respectively) on urinary 1-OHP excretion, though did not show significant differences.…”

Clinical, Cytogenetic and CYP1A1 exon-1 Gene Mutation Analysis of Beedi Workers in Vellore Region, Tamil Nadu

“…The chromosomal damage in the smoker exposed group is almost twice that of controls suggesting the multiplicative effect of smoking and exposure to tobacco dust. In our study, we did not observe any significant association of age, sex and consumption habits with genetic damage (Giri et al, 2012).…”

Skin disease after occupational dermal exposure to coal tar: a review of the scientific literature

“…observed that induction of cytochrome P‐450 enzymes (CYP1A1, CYP1B1), which, as mentioned above, are those that convert BaP to bioactive molecules that bind to the DNA and induce the genetic lesions, reduced the number of BPDE DNA‐adducts. However, another study showed that coal tar workers with genetic polymorphisms of CYP1A1 m1 and m2, which are associated with enhanced enzymatic activity, seem to be susceptible to genetic damage from PAHs . More studies are necessary to describe the exact molecular mechanisms behind coal tar and the latest research data to be interpreted with certainty.…”