Occupational exposure in spraying and application of non-arsenical insecticides has been classified as a probable human carcinogen. The fundamental molecular mechanisms involved the tumor-related genes. This study aimed to investigate the carcinogenesis effects related to chronic exposure to organophosphate (OP) pesticides in pesticide applicators. This was a cross-sectional study conducted on 27 pesticide applicators and 24 matched controls through the period from June to December 2018. The level of acetylcholinesterase (AChE) was determined and the effects of OPs exposure on messenger RNA (mRNA) expression of the DNA-damage responsive genes P53, P21, GADD45a, and MDM2 were determined using real-time quantitative polymerase chain reaction. A significant reduction of serum AChE enzyme activities was observed in chronically exposed subjects in comparison with the control group (p = 0.001). The expression of P53, P21 mRNA was significantly downregulated in the exposed group compared with the healthy nonexposed control group (p < 0.05). Conversely, the expression of MDM2 and GADD45a did not significantly differ between the exposed subjects and the control group (p > 0.05). No significant differences were noted between the exposed and control groups regarding the genotype or allele distributions of P53 Arg72Pro polymorphism. These results suggested that chronic exposure to OP insecticides may have mitogenic and carcinogenicity activity for the exposed cases due to downregulation of P53 and P21 but did not demonstrate any DNA damage properties for the exposed cases, and finally, a regular follow-up of the exposed cases for tumor markers is recommended.
Keywords: GADD45a; MDM2; Organophosphate; P21; P53; carcinogenicity.