Extrahepatic cytochrome P450: role in in situ toxicity and cell-specific hormone sensitivity.

Abstract

It is clear that members of the Cytochrome P450 supergene family are responsible for the majority of activations of procarcinogens to ultimate carcinogens in the body. These procarcinogens include the food mutagens (heterocyclic amines), pesticides, polycyclic aromatic hydrocarbons and nitrosamines. The Cyp P450 profile in a cell can indicate the capacity of that cell to form reactive metabolites. Furthermore, environmental factors, through their action on P450s, influence the fate of procarcinogens in a cell. This is because different isoforms of P450 are regulated differently by ethanol, diet and environmental inducers, have different substrate specificities and different propensity to be inhibited or activated by dietary components. Cyp P450 (through steroid inactivation), can also influence sensitivity of cells to hormones. Age and hormone related regulation of P450 isoforms such as 1A1, 2B1 and 2A3 in the breast suggest that in situ activation of carcinogens and hormone inactivation can occur in the breast. In the brain and endometrium most of the #P450 isoforms remain to be identified.