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

Shiv Kumar Giri,Anil Kumar,Neeraj Aggarwal,Anita Yadav,Sachin Gulati,Ranjan Gupta,Sanjeev Kumar Gautam,Kapil Dev

doi:10.7314/apjcp.2012.13.7.3409

Shiv Kumar Giri, Anil Kumar + Show 6 more

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https://doi.org/10.7314/apjcp.2012.13.7.3409

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Abstract

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 coal-tar workers exposed to PAHs in their work place. 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. 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. 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.

Highlights

Coal-tar workers, workings at coal-tar melting stations and road construction sites routinely expose themselves to a large number of physical or chemical genotoxic agents such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic compounds by inhalation and dermal absorption at their work place (King et al, 1984)
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
In our study we found significant association of CYP1A1 m1 and m2 heterozygous+homozygous variants with genetic damage suggesting that these polymorphisms may modulate the effects of PAH exposure in occupational settings

Summary

Introduction

Coal-tar workers, workings at coal-tar melting stations and road construction sites routinely expose themselves to a large number of physical or chemical genotoxic agents such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic compounds by inhalation and dermal absorption at their work place (King et al, 1984). Monitoring of biological effects as a measure of the internally effective dose is more relevant for assessment of the ultimate health risks such as cancer. Many biomarkers such as chromosomal aberrations, micronuclei, sister chromatid exchanges and comet assay have been developed to estimate exposure and to assess in an early phase the risk of adverse health effects (Wogan, 1992; Van Delft et al, 1998). Micronuclei (MN) index in human cells has become one of the standard cytogenetic endpoints and biomarkers used in genetic toxicology in vivo or ex vivo (Holland et al, 1999). The comet assay (single-cell gel electrophoresis) has become the preferred test for the qualitative and quantitative assessment of DNA damage in single cells and capable of detecting DNA single- and double-strand breaks, alkali-labile sites and incomplete excision repair sites, and genomic structural discontinuities (Singh et al, 1988; Collins, 2004)

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