Cytotoxic and genotoxic activity of 1,3-dichloropropene in cultured mammalian cells.
1,3-Dichloropropene (DCP), a widely used soil fumigant previously found to be carcinogenic in both mice and rats, was evaluated for its cytotoxic and genotoxic effects in cultured rodent and human cells. A reduction of cell viability that was dependent on the dose and the length of treatment was observed with the trypan blue and the neutral red assay in both V79 cells and rat hepatocytes exposed to DCP concentrations ranging from 0.18 to 5.6 mM. In the absence of a metabolic activation system, a dose-dependent frequency of DNA single-strand breaks, that were only partially repaired within 24 hr, was revealed by the alkaline elution technique in V79 cells exposed to subtoxic DCP concentrations. The genotoxicity of DCP was confirmed by the results obtained in metabolically competent primary cultures of both rat and human hepatocytes which displayed similar dose-related amounts of DNA fragmentation and DNA repair synthesis, and showed, in comparison to metabolically deficient V79 cells, a somewhat greater sensitivity to the cytotoxic and DNA-damaging effects of DCP. The increase in the frequency of DNA breaks observed in rat hepatocytes after GSH depletion confirms the role of this tripeptide in DCP detoxification; its reduction in hepatocytes simultaneously exposed to metyrapone is consistent with a cytochrome P450-dependent biotransformation of DCP to more toxic metabolites.
Martelli
A
A
Institute of Pharmacology, University of Genoa, Italy.
Allavena
A
A
Ghia
M
M
Robbiano
L
L
Brambilla
G
G
D000498:Allyl Compounds / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D006801:Humans; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000498:Allyl Compounds; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; C023891:1,3-dichloro-1-propene