CYP polymorphisms and pathological conditions related to chronic exposure to organochlorine pesticides

Docea AO, Vassilopoulou L, Fragou D, Arsene AL, Fenga C, Kovatsi L, Petrakis D, Rakitskii VN, Nosyrev AE, Izotov BN, Golokhvast KS, Zakharenko AM, Vakis A, Tsitsimpikou C, Drakoulis N. Abstract The association between genetic variations in the cytochrome P450 (CYP) family genes and pathological conditions related to long-term exposure to organochlorine compounds (OCs) deserves further elucidation. OCs are persistent organic pollutants with bioaccumulative and lipophilic characteristics. They can act as endocrine disruptors and perturb cellular mechanisms. Prolonged exposure to OCs has been associated with different pathological manifestations. CYP genes are responsible for transcribing enzymes essential in xenobiotic metabolism. Therefore, polymorphisms in these genetic sequences a. alter the metabolic pathways, b. induce false cellular responses, and c. may provoke pathological conditions. The main aim of this review is to define the interaction between parameters a, b and c at a mechanistic/molecular level, with references in clinical cases. KEYWORDS: ARNT, AhR nuclear translocator; AhR, aryl hydrocarbon receptor; CYP450, cytochrome P450; Cytochrome P450; DDE, dichlorodiphenyldichloroethylene; DDT, dichlorodiphenyltrichloroethane; Environmental pollutants; GST, glutathione-S-transferase; Genetic polymorphisms; HCB, hexachlorobenzene; HCH, hexachlorocyclohexane; HPTE, hydroxychlor; MXC, methoxychlor; OBP, organochlorine by-product; OC, organochlorine compound; Organochlorine compounds; PAA, phenoxyacetic acid; PCB, polychlorinated biphenyl; PCDD, polychlorinated dibenzodioxins; PCDF, polychlorinated dibenzofurans; POP, persistent organic pollutant; Pathogenesis; ROS, reactive oxygen species; SNP, single nucleotide polymorphism; TCDD, tetrachlorodibenzodioxin; VCM, vinyl chloride monomer PMID: 28959657 PMCID: PMC5615117 DOI: 10.1016/j.toxrep.2017.05.007 https://www.sechenov.ru/science_and_innovation/repo/?PAGEN_1=11#abstract134940