Mechanisms of multistep carcinogenesis and carcinogen risk assessment.

Mechanisms of multistep carcinogenesis and carcinogen risk assessment.

Many different types of chemical exposures can increase the incidence of tumors in animals and humans, but usually a long period of time is required before the carcinogenic risk of an exposure is manifested. Both of these observations can be explained by a multistep/multigene model of carcinogenesis. In this model, a normal cell evolves into a cancer cell as the result of heritable changes in m...

Cellular and molecular mechanisms of multistep carcinogenesis: relevance to carcinogen risk assessment.

Carcinogenesis is a multistep process involving alterations in at least two distinct classes of genes. Protooncogenes are activated qualitatively or quantitatively in certain tumors, and they appear to act as positive proliferative signals for neoplastic growth. In contrast, tumor suppressor genes are normal genes that must be inactivated or lost for tumor development. When active, tumor suppre...

Aromatic amines: mechanisms of carcinogenesis and implications for risk assessment.

Carcinogenic aromatic amines are widespread and need to be regulated. Genotoxic and non-genotoxic effects are both necessary for tumor development. The common mode of action includes metabolic activation, the reaction of metabolites with nucleic acids and cellular macromolecules as well as toxic effects. The dose-response relationship of irreversible DNA damage is linear down to background conc...

Carcinogen risk assessment.

A molecular biological rationale for the linear nonthreshold dose-response pattern for carcinogenesis is presented based on the mutagenic activation of oncogens as the basis of initiation. The approach assumes that the linear nonthreshold dose pattern at very low doses applies only to tissues that are promoted by intrinsic and extrinsic agents other than the one being modeled, and that risk is ...

Guidelines for Carcinogen Risk Assessment