Topically applied nitropyrenes are potent inducers of cutaneous and hepatic monooxygenases.
The inducibility of skin and liver microsomal cytochrome P-450 dependent aryl hydrocarbon hydroxylase and other monooxygenases by a mixture of nitropyrenes was assessed and compared with the parent non-nitrated compound, pyrene. A single topical application of nitropyrenes to neonatal rats resulted in highly significant induction of aryl hydrocarbon hydroxylase, ethoxycoumarin O-de-ethylase, and ethoxyresorufin O-de-ethylase activities in skin and liver after 24 hours. Inducibility of the skin and liver enzymes was 3.9-5.7 fold and 1.8-10.3 fold respectively. On the other hand, aminopyrine N-demethylase, benzphetamine N-demethylase and epoxide hydrolase activities in the liver were unaffected by topically applied nitropyrenes. Furthermore, treatment with nitropyrenes produced a 1 nm shift to the blue region in the wavelength maximum of hepatic microsomal cytochrome P-450. Topically applied pyrene produced only marginal or no effects on cutaneous and hepatic enzyme activities. Our results suggest that nitration of pyrene, a relatively ineffective enzyme inducer, produces nitropyrenes which are potent inducers of hepatic and cutaneous monooxygenases and they resemble 3-methylcholanthrene in this inducing effect.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System; D004790:Enzyme Induction; D004851:Epoxide Hydrolases / Q000096:biosynthesis; D005260:Female; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010088:Oxidoreductases / Q000096:biosynthesis*; D010105:Oxygenases / Q000096:biosynthesis; D011247:Pregnancy; D011721:Pyrenes / Q000494:pharmacology*; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D013053:Spectrophotometry; D013997:Time Factors
D011721:Pyrenes; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D004851:Epoxide Hydrolases