US EPA

2210966 

Journal Article 

Effects of Antioxidants and of Different Metabolic Activation Systems on Dichlorovinylcysteine-Induced Genotoxicity 

Muller, W; Cojocel, C; Mayer, D 

1990 

1 

Toxicology Letters
ISSN: 0378-4274
EISSN: 1879-3169 

NIOSH/00198955 

53 

1-2 

1-2 

The effects of antioxidants and different metabolic activation systems on dichlorovinylcysteine (DCVC) induced genotoxicity were studied in-vitro. DCVC was tested for mutagenicity in the Amesalmonella assay in strains (TA-100), (TA-1535), and (TA-102) and in Escherichia-coli WP2uvrA trp with or without metabolic activation by liver or renal cortex S9 mix from aroclor-1254 rats and mice and human liver S9 mix. Human lung tumor A549 cells were incubated with 0 or 5 micromolar DCVC in the presence or absence of 0.1 or 10 millimolar (mM) glutathione for 3 hours. DNA damage was assessed by determining the number of DNA single strand breaks and uptake of tritium labeled thymidine. DCVC was not mutagenic in (TA-100) or (TA-1535). DCVC was mutagenic in (TA-102) and WP2uvrA in the presence of S9 mix from all species. Amino-oxyacetic-acid (AOAA) and (+)-cyanidanol-3 had no effect on DCVC mutagenicity. DCVC alone did not induce DNA damage. DCVC plus 10mM glutathione significantly increased the number of single strand breaks and uptake of thymidine when renal cortex S9 mix was present. The authors conclude that the observed differences in DCVC mutagenicity in the Ames Salmonella assay may reflect differences in bacterial beta-lyase activity. Glutathione appears to be involved in the activation of DCVC in the renal cortex.