Urothelial cell DNA adducts in rubber workers†

Abstract

Workers employed in the rubber industry appear to have a significant excess cancer risk in a variety of sites, including cancer of the urinary bladder. In this cross-sectional study, we investigated the occurrence of DNA adducts in exfoliated bladder cells of currently exposed, nonsmoking rubber workers (n = 52) and their relationship with occupational exposure estimates and acetylation phenotype (NAT2). Four DNA adducts were identified, with the proportion of positive samples (e.g., DNA samples with quantifiable levels of a specific DNA adduct) ranging from 3.8 to 79%. The highest proportion of positive samples and the highest relative adduct labeling levels were in workers involved in the production functions "mixing" and "curing," areas with potential for substantial exposure to a wide range of chemical compounds used in rubber manufacturing (P < 0.05 for adducts 2 and/or 3, compared to all other departments). No statistically significant relationships were found between identified DNA adducts and urinary mutagenicity or personal inhalable and dermal exposure estimates. Interestingly, subjects with a fast NAT2 acetylation phenotype tended to have higher levels of DNA adducts. This study suggests that rubber workers engaged in mixing and curing may be exposed to compounds that can form DNA adducts in urothelial cells. Larger studies among rubber workers should be conducted to study in more detail the potential carcinogenicity of exposures encountered in these work areas.

Polycyclic Aromatic Hydrocarbon Exposure, Urinary Mutagenicity, and DNA Adducts in Rubber Manufacturing Workers

“…In addition, we observed elevated bladder DNA adduct levels in previously identified high-risk production functions of compounding, mixing, and curing compared with other departments (7). These results indicated the presence of genotoxic exposures in the contemporary rubber manufacturing industry in the Netherlands.…”

“…However, we found some interaction of acetylation status on the correlation between urinary mutagenicity Table 3. Association between personal inhalable dust, rubber fumes measured as cyclohexane soluble matter, dermal cyclohexane soluble matter exposure, and urinary levels of 1-hydroxypyrene and mutagenicity Results from earlier studies on mutagenic exposures among rubber manufacturing workers have pointed toward the importance of aromatic amine exposure for genotoxic risk in the rubber manufacturing industry as well (7,31). We found no correlation between bladder and blood cell DNA adduct levels, suggesting that the adducts in each case are potentially formed by different agents and/ or by different metabolic actions.…”

“…Sixty nonsmokers were randomly selected from the subpopulation. DNA (>20 Â 10 7 nucleotides) was successfully isolated from exfoliated urothelial cells of 52 subjects as described by Vermeulen et al (7). 32 P-postlabeling was done under conditions of excess radiolabeled ATP.…”

“…Acetylation status was previously found to influence urinary mutagenicity and urothelial cell DNA adducts levels (7,19). Acetylation status was determined by measuring caffeine and its metabolites as described by Grant et al (20).…”

Exposure to inhalable dust and its cyclohexane soluble fraction since the 1970s in the rubber manufacturing industry in the European Union

“…Also, elevated levels of DNA adducts were found in the exfoliated bladder cells of current rubber industry workers 15. These studies suggest the possibility of genotoxic risks in the modern rubber industry.…”