Can the concept of hormesis Be generalized to carcinogenesis?
The concept of hormesis (i.e., low-dose stimulation/high-dose inhibition) has been shown to be widely generalizable with respect to chemical class, animal model, gender, and biological end point. The public health implication of this lack of linearity in the low-dose area of the dose-response curve raises the question of whether low doses of carcinogens will reduce cancer risk. Articles relating to the process of carcinogenesis (i.e., initiation, promotion, tumor development, and progression) were obtained from a recently developed chemical hormesis database and evaluated for their evidence of hormesis. Numerous examples in well-designed studies indicate that U- or J-shaped dose-response relationships exist with respect to various biomarkers of carcinogenesis in different animal models of both sexes. Examples of such J-shaped dose-response relationships in each stage of the process of carcinogenesis were selected for detailed toxicological examination. These results have important implications for both the hazard assessment of carcinogens and cancer risk assessment procedures.
Calabrese
E J
EJ
Department of Environmental Health Sciences, School of Public Health, University of Massachusetts, Amherst, Massachusetts, 01003, USA.
Baldwin
L A
LA
D000818:Animals; D002109:Caffeic Acids / Q000633:toxicity; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D011088:DNA Ligases / Q000378:metabolism; D004147:Dioxins / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000139:chemically induced; D015603:Keratinocytes / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D008628:Mercury / Q000633:toxicity; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009381:Neoplasms, Radiation-Induced; D010634:Phenobarbital / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D012439:Saccharin / Q000633:toxicity; D013270:Stomach / Q000187:drug effects; D013736:Testicular Neoplasms / Q000139:chemically induced; D001743:Urinary Bladder / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D002109:Caffeic Acids; D002273:Carcinogens; D004147:Dioxins; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D008769:Methylnitronitrosoguanidine; D011088:DNA Ligases; D012439:Saccharin; D008628:Mercury; D010634:Phenobarbital