Thresholds for DNA-Reactive (Genotoxic) Organic Carcinogens

Genotoxic thresholds, DNA repair, and susceptibility in human populations.

It has been long assumed that DNA damage is induced in a linear manner with respect to the dose of a direct acting genotoxin. Thus, it is implied that direct acting genotoxic agents induce DNA damage at even the lowest of concentrations and that no "safe" dose range exists. The linear (non-threshold) paradigm has led to the one-hit model being developed. This "one hit" scenario can be interpret...

Are genotoxic carcinogens more potent than nongenotoxic carcinogens?

In this report we have raised the question whether genotoxic carcinogens are more potent than nongenotoxic carcinogens when studied in long-term carcinogenicity assays in rodents. To build a large database of compounds for which both carcinogenicity and genotoxicity had been investigated, we have used a database produced by Gold and co-workers for carcinogenic potency data (975 chemicals) and a...

Hormesis in Carcinogenicity of Non-genotoxic Carcinogens

Recently the idea of hormesis, a biphasic dose-response relationship in which a chemical exerts opposite effects dependent on the dose, has attracted interest in the field of carcinogenesis. With non-genotoxic agents there is considerable experimental evidence in support of hormesis and the present review highlights current knowledge of doseresponse effects. In particular, several in vivo studi...

Interpretation of Margins of Exposure for Genotoxic Carcinogens Final Report

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...