Abstract
Similarities and differences in the P-450 hemoprotein-dependent benzpyrene hydroxlyase systems of the liver and intestinal mucosa of untreated and 3-methylcholanthrene-treated rats were evaluated by comparing the effects of selected inhibitors of the systems (ethanol. 3-metimyl-4-methylaminoazobenzene, SKF 525-A, ethylmorphine, aniline and carbon monoxide), by relating kinetic constants for the hydroxylation of 3,4-benzpyrene by the systems, and by observing spectral differences in the P-450 hemoproteins of the systems as revealed by difference spectra of their complexes of reduced microsomal P-450 hemoprotein with ethyl isocyanide. Inhibitors were also employed in the characterization of adrenal benzpyrene hydroxylase. Two P-450 hemoproteins exist in liver, cytochrome P-450. which comprises the preponderance of P-450 hemoprotein in the livers of untreated animals, and cytochrome P1-450 (P-448), which appears in the liver when 3-methylcholanthrene and other polycyclic hydrocarbons are administered. Using criteria defined by inhibition, kinetic and spectral parameters, it was proposed that two benzpyrene hydroxylases can exist in liver, one identified by its utilization of cytochrome P-450 as its terminal the oxidase the by its utilization of cytochrome P1-450. The P-450 benzpyrene hydroxylase system predominates in the livers of untreated animals. The P-450 benzpyrene hydroxylase system predominates in the livers of 3-methylcholanthrene-treated animals. In contrast, the P1-450 benzpyrene hydroxylase system predominates in the intestinal mucosa of both treated and untreated animals and, of the two hemoproteins, may in fact be the only present in this tissue. It was concluded that adrenal benzpyrene hydroxylase is different from that in liver and intestinal mucosa, and that 3-methylcholanthrene does not induce quantitative or qualitative changes in adrenal benzpyrene hydroxylase. The P1-450 benzpyrene hydroxylase system is visualized as functioning primarily in portals of entry (intestine, skin, lung) and in the liver where it mediates the biotransformation of noxious exogenous compounds, particularly those causing its induction.
Footnotes
- Received October 12, 1972.
- Accepted February 28, 1973.
- © 1973 by The Williams & Wilkins Co.
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