Evaluation of the Association Between Reproductive Hazards of Vinyl Chloride and KRAS Gene Mutations in Adult Male Factory Workers

Abstract

Vinyl chloride (VC) is a monomer of polyvinyl chloride (PVC) which is among one of the most common synthetic polymers used in manufacturing of different plastic products across the world. Like other plasticizers, it also acts as an endocrine disrupting chemical (EDC) and can disrupt normal functioning of hypothalamic-anterior pituitary gonadal axis (HPG axis). It is also a renowned carcinogen and may be the possible cause of mutations and (KRAS) gene is one of the most frequently mutated gene due to VC exposure. Current experiment was performed to evaluate the association between reproductive hazards of VC as EDC and mutations of KRAS gene. Adult male factory workers (n=125) were enrolled in the study and were organized into five groups; exposed groups (n=95) and control group (n=30). Individuals of the first group (n=36) have an exposure between 1-5 years. Individuals with an exposure of 6-10 years were grouped into the second group (n=32). Third group (n=17) and fourth group (n=10) members have an exposure between 11-15 and 16-20 years respectively. Individuals with no exposure were classified into the control group (n=30). Blood samples were obtained from participants for mutational analysis and plasma was separated and stored for hormonal analysis. Mutational analysis was performed separately for exon 1 and exon 2 of KRAS gene. Results of present study revealed a significant decrease of testosterone concentration in first and second groups having an exposure of 1-5 years and 6-10 years respectively but a non-significant decrease was noticed in third and fourth groups having an exposure of 11-15 and 16-20 years respectively. KRAS mutations were also found in members of all the VC exposed groups. Eighteen samples were found mutated of exon 1 out of 95 VC exposed and 14 samples of exon 2 out of 95 samples were mutated irrespective of testosterone levels. In conclusion, our findings suggest that VC exposure reduces testosterone concentration in adult male workers but prolong exposure to VC has non-significant affect on testosterone concentration. Current findings also demonstrated that VC induces KRAS mutations regardless of the testosterone levels in adult male workers. Therefore, present findings did not show any association between testosterone concentration and mutations of KRAS gene