title: A cancer risk model with adaptive repair.
abstract: The cancer risk model described herein first appeared in 1982. The model provides a plausible mechanism with biological underpinnings that might reasonably explain observed phenomena in cancer dose-response studies that are not being addressed by the risk models currently in use. This article is a summary and explanation of the features of the model that relate to hormesis. Data from several saccharin studies served in large part to motivate the original research, and were used to illustrate beneficial low-dose effects that could be explained by the model. The model itself is a function of linear ratios of the administered dose x. Linear ratios arise naturally from non-linear Michaelis-Menten kinetics, as described in the next section. The one-hit cancer risk model is used to illustrate the hormetic concepts brought out by linear ratios. The one-hit model is modified to account for repair and for non-linear kinetics, by using a linear ratio of the administered dose instead of the actual administered dose, and by expressing the probability that a 'hit' is repaired as a linear ratio of the administered dose. The phenomenon of hormesis - or low-dose beneficial effects-has been widely observed and accepted. Yet none of the cancer risk models currently in wide use have attempted to accommodate hormetic effects. The modified one-hit model developed herein does not attempt to account for elimination or detoxification, but nevertheless it provides plausible explanations for certain classes of observed hormetic phenomena associated with experimental testing of carcinogenic substances in animals.
authors.affiliation: Research Statistics, Inc., Houston, Texas 77265-5231, USA.
authors.forename: T
authors.initials: T
authors.lastname: Downs
authors.forename: R
authors.initials: R
authors.lastname: Frankowski
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D018570:Risk Assessment