Induction of morphological transformation and unscheduled DNA synthesis in Syrian hamster embryo fibroblasts by hexachlorobutadiene and its putative metabolite pentachlorobutenoic acid.
Hexachloro-1,3-butadiene (HCBD) is a well known environmental carcinogen. The genotoxic properties of HCBD and its monooxidation product pentachloro-3-butenoic acid (PCBA) were investigated by comparative induction of unscheduled DNA synthesis (UDS) and morphological transformation in the same cell system (Syrian hamster embryo fibroblasts). HCBD and PCBA induce unscheduled DNA synthesis both in the presence and absence of an exogenous metabolizing system. The lowest effective dose for UDS induction is smaller for PCBA (1 microgram/ml) than for HCBD (2 micrograms/ml). The intensity of UDS induction is increased about 3-fold for both compounds after metabolic activation. HCBD and PCBA induce morphological transformation. The lowest effective dose for transformation differs considerably between PCBA (0.8 micrograms/ml) and HCBD (10 micrograms/ml). The results are indicative of a genotoxic mechanism for the carcinogenic actions of HCBD and PCBA.
D000818:Animals; D002070:Butadienes / Q000378:metabolism / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000473:pathology; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis*; D004622:Embryo, Mammalian; D005347:Fibroblasts; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains
D002070:Butadienes; D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; C042110:2,2,3,4,4-pentachloro-3-butenoic acid; D004247:DNA; C001335:hexachlorobutadiene