Potency of carcinogens derived from covalent DNA binding and stimulation of DNA synthesis in rat liver.
In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrachloride (all known to be genotoxic via DNA binding) did not affect cell division, whereas several hepatocarcinogens known not to bind to DNA (alpha-HCH, clofibrate, and 2,3,7,8-tetrachlorodibenzo-p-dioxin) gave rise to a dose-dependent stimulation of liver DNA synthesis within 24 h. An equation combining the influences of mitotic stimulation, expressed as dose required to double the control level of DNA synthesis, and DNA binding potency, expressed as the Covalent Binding Index, correlated well with the carcinogenic potency for both classes of hepatocarcinogens.
D000818:Animals; D001667:Binding, Competitive; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism
D002250:Carbon Radioisotopes; D002273:Carcinogens; D004247:DNA; D013936:Thymidine