Genetic Polymorphisms and Pesticide-Induced DNA Damage: A Review

Abstract

The drastic increase in pesticide applications makes human exposure inevitable either through environment or occupation. Pesticide toxicity causes many adverse health effects through a number of pathways leading to DNA damage, mutations and cancers. Nevertheless, there is heterogeneity in the degree of toxicity among individuals due to the influence of genetic polymorphisms on xenobiotic metabolizing enzymes (XMEs) that modulate the biological process. Thus, study of the most common polymorphic genes coding for the enzymes involved in pesticide metabolism (such as cytochrome P450, Glutathione S-transferases, N-acetyltransferase and paraoxonase) may help determine individual’s susceptibility to pesticide toxicity. In this review, we give an overview of some recent developments in the field of genetic polymorphism and pesticide-related DNA damage, including probable biomarkers that may uncover genome susceptibility to pesticide toxicity. We have tried to create a connection between DNA polymorphism and cancer onslaught globally. It is envisaged that knowledge on this line would improve our understanding of facilitating the association between genotype and phenotype in cancer biology.

Case-Control Study of the Association between Single Nucleotide Polymorphisms of Genes Involved in Xenobiotic Detoxification and Antioxidant Protection with the Long-Term Influence of Organochlorine Pesticides on the Population of the Almaty Region

“…Molecular epidemiological studies of genetic polymorphisms detected the involvement of xenobiotic detoxification and antioxidant protection genes in developing a wide range of multifactorial diseases, including oncological, cardiovascular, neurodegenerative, and autoimmune diseases [ 4 , 26 , 27 ]. Data indicate the possibility of using polymorphic variants of xenobiotic metabolism genes as molecular genetic markers, which show the individual sensitivity of the population to adverse environmental influences [ 21 ].…”

“…Focusing on the medical status of the population exposed to pesticide contamination (cardiovascular diseases, gastrointestinal diseases, cancer, autoimmune diseases, diabetes mellitus, hypothyroidism, etc. ), we chose SNPs of xenobiotic detoxification genes ( CYP1A1 , CYP2B6 , CYP2D6 , CYP2C19 , GSTM1 , GSTT1 , GSTP1 , NAT2 ) [ 14 , 21 , 22 ] and antioxidant protection ( GCLC , GCLM , GPX4 , PON1 , PON2 , PON3 , NQO1 , SOD1 , SOD2 , SOD3 , AKR1B10 , AKR1C1 , APOE , NFE2 , NFE2L1 , NFE2L2 , NFE2L3 , SRXN1 , TXNRD1 , UCP3 ) [ 9 , 13 , 23 , 24 , 25 , 26 , 27 ], mutations which are associated with these diseases. Trying to answer the question of whether SNPs of xenobiotic detoxification genes and the genes of the antioxidant system influence the development of different diseases in selected populations that are chronically exposed to organochlorine pesticides, we conducted a case-control study to assess the health implications of these SNPs.…”