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Model studies in cytochrome P-450 mediated toxicity of halogenated compounds: radical processes involving iron porphyrins

Journal Article · · Environ. Health Perspect.; (United States)
DOI:https://doi.org/10.1289/ehp.856453· OSTI ID:5148540
Haloalkane toxicity originates from attack on biological targets by reactive intermediates derived from haloalkane metabolism by a hemoprotein, cytochrome P-450. Carbon-centered radicals and their peroxylderivatives are most likely involved. The reactions of iron porphyrin - a model for cytochrome P-450 - with various carbon-centered and peroxyl radicals generated by pulse radiolysis are examined. Competition between iron porphyrin and unsaturated fatty acids for attack by peroxyl radicals is pointed out. These kinetic data are used to derive a model for toxicity of haloalkanes with particular attention to carbon tetrachloride and halothane. The importance of local oxygen concentration and structural arrangement of fatty acids around cytochrome P-450 is emphasized. 56 references.
Research Organization:
Museum National d'Histoire Naturelle, Paris, France
OSTI ID:
5148540
Journal Information:
Environ. Health Perspect.; (United States), Journal Name: Environ. Health Perspect.; (United States) Vol. 64; ISSN EVHPA
Country of Publication:
United States
Language:
English

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