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Benzo(a)pyrene Phenol Production by Perfused Rat Liver and Its Inhibition by Ethanol¹

Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514 [L. A. R., P. M., R. G. T.], and Department of Pharmacology, University of Maryland School of Medicine, Baltimore, Maryland 21201 [F. C. K.]

A rapid and inexpensive method has been developed to estimate rates of benzo(a)pyrene phenol production by perfused rat liver. This method is based on the measurement of benzo(a)pyrene phenols utilizing a simple fluorometric procedure. Within 2 to 3 min after infusion of benzo(a)pyrene bound to serum albumin, phenols are excreted into the perfusate, primarily as glucuronide and sulfate conjugates. Maximal rates of phenol release were 8 to 10 nmol/g/hr in livers from control rats and 40 to 42 nmol/g/hr in livers from 3-methylcholanthrene-treated rats. Fasting of 3-methylcholanthrene-treated rats for 24 hr prior to perfusion experiments did not affect either the rate of phenol production or the extent of their conjugation. Ethanol (20 mM) inhibited rates of phenol formation by 50% in livers from fasted, 3-methylcholanthrene-treated rats but had no effect on benzo(a)pyrene hydroxylase activity in isolated hepatic microsomes. These data indicate that ethanol inhibits phenol formation from benzo(a)pyrene in intact liver, probably by diminishing the supply of the cofactor reduced nicotinamide adenine dinucleotide phosphate.

¹ Supported in part by Grants CA-30137, CA-23080, and CA-20807 from the National Cancer Institute.

² Present address: Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City, Okla. 73190. To whom requests for reprints should be addressed.

³ Recipient of Research Scientist Development Award AA-00033.

Received 8/ 3/81. Accepted 1/29/82.