The stimulation of hydroxylation by carcinogenic and non-carcinogenic compounds

The relationship between hepatic microsomal biphenyl 2-hydroxylase, 4-hydroxylase and urinary glucaric acid excretion in the rat

“…Treatment of rats with PB caused 1.5-2- (4) 8.50 ± 1. 86 (4) 13.96 ± 2.66 (4) 11.16 ± 0.71 (6) 10.05 ± 2.23 (7 In CCl 4-pretreated rats, urinary glucaric acid excretion, biphenyl 2-and 4-hydroxylase activities were decreased by 53%, 70%, 37% of control, respectively. On the.…”

The effects of benzopyrene and safrole on biphenyl 2-hydroxylase and other drug-metabolizing enzymes

“…Mean percentage increases in enzyme activity for six animals are shown. Significant increases in enzyme activity (P<0.05) were detectable after 4h only for biphenyl 2-hydroxylase. been shown to occur in vitro after 10min preincubation with benzopyrene or 3-methylcholanthrene (Bridges et al, 1973), but after intraperitoneal administration of similar aromatic-hydrocarbon carcinogens induction of biphenyl 2-hydroxylase activity has been shown to occur only after 24h (Creaven & Parke, 1966). In an attempt to correlate these two observations, benzopyrene, safrole or phenobarbitone was administered intraperitoneally to rats, the animals were killed at intervals between 15min and 48h after administration and the activities of biphenyl 2and 4-hydroxylase and other related enzymes determined.…”

“…Pretreatment of rats with various foreign compounds produce different effects on the stimulation of the two modes ofhydroxylation of biphenyl (Creaven & Parke, 1966;Parke & Rahman, 1970). Phenobarbitone and other non-carcinogenic compounds administered to the rat either selectively stimulate biphenyl 4-hydroxylation or have no enhancing effect, whereas carcinogenic compounds such as 3-methylcholanthrene, 3,4-benzopyrene and safrole preferentially stimulate the 2-hydroxylation of biphenyl with a smaller or no effect on biphenyl 4-hydroxylation.…”

Mechanisms and consequences of the induction of microsomal enzymes of mammalian liver

“…The induction ofcytochrome P-450 and the hepatic microsomal drug-metabolizing enzymes by fi-ionone also involves synthesis de novo, but the increases in enzymic activities that result from pretreatment with safrole and isosafrole are due only in part to increased enzyme synthesis. With the substrate biphenyl it has been shown that hydroxylation in the 4-position may be induced by both drugs and carcinogenic polycyclic hydrocarbons, whereas hydroxylation in the 2position is increased primarily by the carcinogens (Creaven & Parke, 1966). Safrole, a component of oil of sassafras and other essential oils and flavours, is a weak hepatocarcinogen (Epstein et al, 1970).…”