Molecular Epidemiology Studies on Occupational and Environmental Exposure to Mutagens and Carcinogens, 1997-1999

Abstract

Molecular epidemiology is a new and evolving area of research, combining laboratory measurement of internal dose, biologically effective dose, biologic effects, and influence of individual susceptibility with epidemiologic methodologies. Biomarkers evaluated were selected according to basic scheme: biomarkers of exposure-metabolites in urine, DNA adducts, protein adducts, and Comet assay parameters; biomarkers of effect-chromosomal aberrations, sister chromatid exchanges, micronuclei, mutations in the hypoxanthine-guanine phosphoribosyltransferase gene, and the activation of oncogenes coding for p53 or p21 proteins as measured on protein levels; biomarkers of susceptibility-genetic polymorphisms of genes CYP1A1, GSTM1, GSTT1, NAT2. DNA adducts measured by 32P-postlabeling are the biomarker of choice for the evaluation of exposure to polycyclic aromatic hydrocarbons. Protein adducts are useful as a biomarker for exposure to tobacco smoke (4-aminobiphenyl) or to smaller molecules such as acrylonitrile or 1,3-butadiene. Of the biomarkers of effect, the most common are cytogenetic end points. Epidemiologic studies support the use of chromosomal breakage as a relevant biomarker of cancer risk. The use of the Comet assay and methods analyzing oxidative DNA damage needs reliable validation for human biomonitoring. Until now there have not been sufficient data to interpret the relationship between genotypes, biomarkers of exposure, and biomarkers of effect for assessing the risk of human exposure to mutagens and carcinogens. Key words: air pollution, benzene, biomarkers, coke oven, genotypes, occupational exposure, PAHs, pesticides, tobacco smoke. -Envwron Health Perspect 1 08(suppl 1):57-70 (2000). http.//ehpnetl. niehs. nih.gov/docs/2000/suppl-1/57-70sram/abstract. html A new and evolving area of research termed molecular epidemiology attempts to merge sophisticated and highly sensitive laboratory methods (many of them developed during the recent revolution in molecular biology) with analytical epidemiologic methods. Molecular epidemiology bridges basic research in molecular biology and studies of human cancer causation by combining laboratory measurement of internal dose, biologically effective dose, biologic effects, and the influence of individual susceptibility with epidemiologic methodologies (1). The most common view is that the approach represents a natural convergence of molecular biology and epidemiology (2).The number of biomarkers available for evaluating genetic and cancer risk in humans is quite large. Their utility-for human biomonitoring is suggested by the well-known paradigm of environmentally induced cancer, which represents end points for assessing the entire spectrum of human-genotoxicant interactions (3). These biomarkers begin with exposure and include absorption, metabolism, distribution, critical target interaction (i.e., DNA damage and repair), genetic changes, and finally, disease, which is the province of traditional epidemiology. The development of biomarkers has given rise to the field of ...

Genotoxic damage in mine workers exposed to diesel exhaust, and the effects of glutathione transferase genotypes

“…As many of the compounds in diesel exhaust are bio-transformed to DNA-damaging agents, genetic differences in enzymes involved in the biotransformation have been found to influence the biomarker level [21]. Previous studies have shown inconsistent effects of genotypes on biomarkers of exposure to environmental pollutants and the consequences of this exposure [20,22,23]. Chromosome aberrations were increased in bus drivers with the null genotype of GSTM1 [17] and a higher DNA-adduct level was found in mothers with the GSTM1-null genotype, exposed to varying amounts of environmental pollution in the Czech Republic [24].…”

Stability and Intra-Individual Variation of Urinary Malondialdehyde and 2-Naphthol

“…Generations of epidemiologists, physicians, and scientists have used biomarkers to study a variety of conditions. Especially, biomarkers of internal dose and early biological effects as a biomarker of oxidative stress have been used in epidemiological studies [1]. Although a number of cohort studies have collected and preserved various biospecimens for use in molecular and genetic epidemiological studies [2,3], it is surprising that there has been little documentation concerning the intra-person variance and inter-person variance reliability associated with biomarkers [4].…”

Cytogenetic study of traffic policemen occupationally exposed to vehicle Exhaust in Erbil City/ Iraqi Kurdistan Region

“…The composition of automobile exhaust is complex and generally contains carbon monoxide, nitrogen oxides, particulates and polycyclic aromatic hydrocarbons (PAHs), nitroaromatics, benzene, 1,3-butadiene, sulfur dioxide and lead (4). Different biomarkers have been used to assess exposure to genotoxic compounds in general and occupational environment, ranging from the presence of mutagenic activity in urine to the induction of chromosomal damage in target and surrogate tissues (5).The hazardous traffic fumes contain a vari¬ety of pollutants which can cause respiratory problems and other systemic diseases including cancer (6). Traffic policemen exposed to vehicular emissions, work in noisy and polluted environment.…”