ONE-HIT MODEL

The one-hit model of carcinogenesis is a doseresponse model based on the assumption that only one genetic change is required to transform a normal cell into a cancer cell, and that any dose of a carcinogen presents a risk of cancer. Only at zero dose is there zero risk. In theory at least, even a single molecule of a carcinogen could turn a normal cell cancerous. The probability of the transformation of a normal cell into a cancer cell, according to the one-hit model, follows a Poisson probability distribution.

The one-hit model is generally recognized to be an overly simplistic representation of the biological process of carcinogenesis. Carcinogenesis is a multistep process, with several genetic changes required to produce a tumor cell. Furthermore, it is highly unlikely that a single molecule of a substance would be biologically capable of causing cancer. Carcinogens have an effective threshold for their activity because of the body's ability to detoxify chemicals, repair cell damage, and otherwise protect itself. However, for regulatory purposes, exposure to a single molecule of a carcinogen is sometimes equated with a single effective dose. That is an assumption of the one-hit process in forming regulatory policy that is health protective because it is likely to over-estimate the probability that a substance will produce cancer.

Gail Charnley

(see also: Cancer; Carcinogen; Carcinogenesis; Genetics and Health; Risk Assessment, Risk Management; Toxicology )