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Toxicology

Critical appraisal of the expression of cytochrome P450 enzymes in human lung and evaluation of the possibility that such expression provides evidence of potential styrene tumorigenicity in humans.


PMID 18951947

Abstract

Styrene is widely used with significant human exposure, particularly in the reinforced plastics industry. In mice it is both hepatotoxic and pneumotoxic, and this toxicity is generally thought to be associated with its metabolism to styrene oxide. Styrene causes lung tumors in mice but not in rats. The question is how the tumorigenic effect in mouse lung may relate to the human. This review examines the comparison of the metabolic activation rates (1) between the liver and lung and (2) for the lung, between the rodent and human. Emphasis is placed on the specific cytochromes P450 present in the lungs of humans and what role they might play in the bioactivation of styrene and other compounds. In general, pulmonary metabolism is very slow compared to hepatic metabolism. Furthermore, metabolic rates in humans are slow compared to those in rats and mice. There is a wide difference in what specific cytochromes P450 investigators have reported as being present in human lung which makes comparisons, both inter-species and inter-organ, difficult. The general low activity for cytochrome P450 activity in the lung, especially for CYP2F1, the human homolog for CYP2F2 which has been identified in mice as being primarily responsible for styrene metabolism, argues against the hypothesis that human lung would produce enough styrene oxide to damage pulmonary epithelial cells leading to cell death, increased cell replication and ultimately tumorigenicity, the presumed mode of action for styrene in the production of the mouse lung tumors.