1989
DOI: 10.1073/pnas.86.20.7696
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Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines.

Abstract: Aromatic amines are well known as occupational carcinogens and are found in cooked foods, tobacco smoke, synthetic fuels, and agricultural chemicals. For the primary arylamines, metabolic N-oxidation by hepatic cytochromes-P-450 is generally regarded as an initial activation step leading to carcinogenesis. The metabolic activation of 4-aminobiphenyl, 2-naphthylamine, and several heterocyclic amines has been shown recently to be catalyzed by rat cytochrome P-450ISF-G and by its human ortholog, cytochrome P-45OP… Show more

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Cited by 568 publications
(354 citation statements)
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“…This has been shown in a GWAS of blood metabolites and of caffeine metabolites 27, 28. Caffeine is metabolized primarily by the enzyme CYP1A2 29, but does not inhibit nicotine pharmacokinetics in‐vivo nor does it alter cigarette consumption 25, 30. For example, when given caffeine at a high dose (12 mg/kg/day, approximately 800 mg per person, relative to average daily consumption of 200 mg) there was no effect on nicotine or cotinine plasma levels or on nicotine intake, cigarettes smoked or grams of tobacco burned 23; therefore, caffeine was not investigated further as a potential CYP2A6 inhibitor.…”
Section: Discussionmentioning
confidence: 87%
“…This has been shown in a GWAS of blood metabolites and of caffeine metabolites 27, 28. Caffeine is metabolized primarily by the enzyme CYP1A2 29, but does not inhibit nicotine pharmacokinetics in‐vivo nor does it alter cigarette consumption 25, 30. For example, when given caffeine at a high dose (12 mg/kg/day, approximately 800 mg per person, relative to average daily consumption of 200 mg) there was no effect on nicotine or cotinine plasma levels or on nicotine intake, cigarettes smoked or grams of tobacco burned 23; therefore, caffeine was not investigated further as a potential CYP2A6 inhibitor.…”
Section: Discussionmentioning
confidence: 87%
“…The maturation of CYP1A2 was delayed compared to other cytochrome P450 isoforms (Cresteil 1998;Sonnier & Cresteil 1998). Using caffeine N-3-demethylation in vitro as a marker for CYP1A2 (Butler et al 1989), Cazeneuve et al (1994) similarly showed a rise in CYP1A2 activity during this period, reaching a plateau at around 120 days.…”
Section: Cytochrome P450 In the Neonatal Human Livermentioning
confidence: 92%
“…CYP1A2 is of toxicological importance because it metabolizes several drugs and carcinogens (Butler et al, 1989). The gene seems to be dispensable since CYP1A2 knock-out mice are viable and fertile (Liang et al, 1996).…”
Section: Commentsmentioning
confidence: 99%