Exposure to epichlorohydrin and dimethylformamide, glutathione S-transferases and sister chromatid exchange frequencies in peripheral lymphocytes

Abstract

Workers in epoxy resin, synthetic leather, and printed circuit board manufacturing plants are exposed to epichlorohydrin (ECH), or dimethylformamide (DMF), or both. ECH, an alkylating agent, has been shown to cause malignancy in animals, but its genotoxicity in humans is unclear. DMF is a well-known hepatotoxic chemical, although evidence of its genotoxicity in humans is also limited. In this study, we examined the effects of exposure to ECH and DMF on sister chromatid exchange (SCE) in plant workers, in order to examine the genotoxicity of these two agents. Because the genotoxicity of certain agents can be modulated by metabolic traits, we also investigated influence of the glutathione S-transferase (GST) micro (GST M1) and GST theta (GST T1) genes on the genotoxicity of ECH and DMF. A total of 85 male plant workers were included in this study. The subjects were divided into five exposure groups, based on their job titles and the airborne ECH and DMF concentrations in their areas of work. A questionnaire was administered to obtain detailed occupational, smoking, alcohol consumption, and medication histories. Standardized cytogenetic methods were used to determine the frequency of sister chromatid exchange (SCE) in peripheral blood lymphocytes. GST M and GST T1 genotypes were identified using polymerase chain reaction (PCR). In analysis, smoking was significantly associated with increased SCE frequency (P<0.01). Workers with high ECH exposure also had significantly higher SCE frequencies than those with low or no ECH exposure (P<0.05). However, DMF exposure was not associated with SCE frequency. The GST M1 null genotype was also found to be associated with an increased SCE frequency (P = 0.06). We conclude that ECH exposure may be associated with genetic toxicity and that DMF does not appear to be genotoxic.

XRCC1 , CYP2E1 and ALDH2 genetic polymorphisms and sister chromatid exchange frequency alterations amongst vinyl chloride monomer-exposed polyvinyl chloride workers

“…68-12-2). Our previous study was unable to demonstrate any association between DMF exposure and SCE frequency alteration in peripheral lymphocytes from DMF-exposed workers (Cheng et al 1999). Evidence from a comprehensive mutagenicity study, including an Ames test, indicates DMF is not a mutagen (Antoine et al 1983).…”

“…Many studies have also shown that smoking can cause an increased SCE frequency (Hedner et al 1982;Sarto et al 1985;Cheng et al 1999;Duell et al 2000). Cigarette smoke contains a variety of known carcinogens, including polycyclic aromatic hydrocarbons (PAHs), aldehyde derivates, and vinyl chloride (Hoffmann et al 1976).…”

Decreased Lung Function Associated With Occupational Exposure to Epichlorohydrin and the Modification Effects of Glutathione S-Transferase Polymorphisms

“…19 Our previous report showed that GSTM1 null genotype was associated with increased SCE frequency in ECH-exposed workers. 9 This study suggests that ECH workers with susceptible genotypes (GST M1 null-type) have increased respiratory damage, including small airways and obstructive lung function. The GSTM1 null genotype was significantly associated with decreased average MMEF value, decreased average FEV 1 value, and decreased average FEV 1 / FVC value.…”

“…8 Our previous report showed GSTM1 null genotype was found to be associated with increased SCE frequency in ECH-exposed workers. 9 Thus, ECH workers with susceptible GSTM1 could be associated with increased respiratory function damage. Another previous study also suggested that obstructive lung abnormalities and small airway lung damage were associated with ECH exposure.…”

Metabolic and DNA Repair Variations in Susceptibility to Genotoxins

“…Positive results on indicator/genotype interactions have been reported for SCEs and genotype ALDH2 with low detoxifying activity, alone or in combination with genotype CYP2E1 with high activity, in exposure to vinyl chloride monomer (VCM) (10), or in combination with GSTM1 null in exposure to epichlorohydrin (163). Morimoto and Takeshita (183) found increased SCE frequencies in smokers who were also habitual drinkers with genotype ALDH2 * 2/ * 2 and * 1/ * 2, with low enzyme activity.…”