Effect of 1-m-tolueneazo-2-naphthol on hepatic drug metabolism. I. Induction of cytochrome P-448.

Abstract

Treatment of rats with 1-m-tolueneazo-2-naphthol (mTAN) caused marked increase in liver weight, microsomal 7-ethoxycoumarin O-deethylase activity and cytochrome P-450 content, with 2 nm hypochromic shift in CO difference spectrum. It decreased NADPH-cytochrome c reductase and aminopyrine N-demethylase activities. Treatment of 3-methylcholanthrene nonresponsive DBA/2 strain of mice with this azo compound resulted in a limited (1.5 fold) induction of cytochrome P-450 compared to 2.5 fold induction in responsive C57BL/6 strain of mice. The major species of liver microsomal P-450 from m-TAN treated rats was purified. This species of P-450 has a Solet peak at 416 nm in the absolute oxidized spectrum, 410 nm in the reduced spectrum and 447 nm in the spectrum of ferrous P-450-CO complex. This species of P-450 is spectrally indistinguishable from cytochrome P-448 induced by 3-methylcholanthrene. As an inducer of cytochrome P-450, m-TAN is similar to 3-methylcholanthrene with its potency equals to or exceeding that of 3-methylcholanthrene. It differs in that it causes marked increase in liver weight and decrease in NADPH-cytochrome c reductase activity.