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Current Topics in Toxicology   Volumes    Volume 2 
The importance of cytochromes P450 in chemical toxicity: structure-activity considerations
David F. V. Lewis, Costas Ioannides
Pages: 25 - 32
Number of pages: 8
Current Topics in Toxicology
Volume 2 

Copyright © 2005 Research Trends. All rights reserved

P450 enzymes have been implicated in the toxicity of organic chemicals, active through a variety of mechanisms. In particular, CYP1 and CYP2E enzymes are most closely associated with the metabolic activation of pro-carcinogens and other toxicants in animal models. The majority of definite human carcinogens are either direct-acting electrophiles or are metabolically activated by P450 enzymes, especially those of the CYP1 family.  Electronic and molecular structural features of organic chemicals appear to pre-dipose them either to activation by one P450 or detoxification by an alternative enzyme.  Moreover, the rate of P450-mediated metabolism can be linked quantitatively to frontier orbital parameters, whereas CYP1 induction potency appears to be determined by a combination of molecular shape and electron activation.
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