Trihalomethanes as initiators and promoters of carcinogenesis.
Chloroform and other trihalomethanes are contaminants of drinking water that have been demonstrated to be carcinogenic in laboratory animals. Determination of the mechanism of carcinogenicity of chloroform is required so that the animal data can be extrapolated to estimate the human health hazard. The extent of the binding of chloroform to rat liver and kidney DNA was approximately 0.1% the level of binding found for dimethylnitrosamine. Neither chloroform nor bromoform, in contrast to diethylnitrosamine-initiated GGTase-positive foci in either intact or partial hepatectomized rats, promoted with phenobarbital. Tumor-promoting activity of chloroform was indicated by the slight significant increase, compared to untreated controls, in the incidence of GGTase-positive foci in rats initiated with diethylnitrosamine (DENA) followed by the administration of chloroform twice weekly for a total of 15 doses. In this study, rats administered only the DENA or the chloroform did not contain an increased incidence of GGTase-positive foci compared to untreated controls. However, the incidence of foci in the group that received DENA followed by chloroform was not statistically different from that in either the group that received only the DENA or only the chloroform. In conclusion, we were unable to demonstrate tumor-initiating activity for chloroform, and the tumor-promoting activity of chloroform indicated by our results requires further confirmation.
D000818:Animals; D002273:Carcinogens; D002725:Chloroform / Q000032:analysis / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D005260:Female; D006842:Hydrocarbons, Brominated / Q000032:analysis / Q000633:toxicity; D006846:Hydrocarbons, Halogenated / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D022882:Trihalomethanes
D002273:Carcinogens; D006842:Hydrocarbons, Brominated; D006846:Hydrocarbons, Halogenated; D022882:Trihalomethanes; D002725:Chloroform; D004247:DNA; C015044:bromoform