Carcinogenic risk assessment: are there dose thresholds for carcinogens?
While it has been generally accepted that genotoxic carcinogens have no dose threshold for their carcinogenic potential, there is increasing evidence that very low doses in fact are incapable of inducing tumours or preneoplastic lesions. Thus not only so-called epigenetic 'non-genotoxic' compounds like phenobarbital and benzene hexachloride, but also unequivocally genotoxic carcinogens like the heterocyclic amines, 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline and amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and the nitrosamines diethylnitrosamine, and dimethylnitrosamine, may exhibit a practical dose threshold below which they do not induce histopathologically assessable lesions. Some form of physiological adaptation may thus be expected to occur in response to low doses of all types of DNA-damaging agents. With 'non-genotoxic' agents there may even be hormesis or paradoxical protection at very low dose.
Fukushima
Shoji
S
Japan Bioassay Research Center, Japan Industrial Safety and Health Association, Hadano, Kanagawa, Japan. s-fukushima@jisha.or.jp
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects*; D004052:Diethylnitrosamine / Q000633:toxicity*; D005982:Glutathione Transferase / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009152:Mutagenicity Tests; D010634:Phenobarbital / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D018570:Risk Assessment
D002273:Carcinogens; D004052:Diethylnitrosamine; D005982:Glutathione Transferase; D010634:Phenobarbital