Mechanisms of cancerogenesis inhibition. II. The aminophenols and their oxidation products.
The protective effect exerted by a series of aminophenols (12 compounds) against in vitro DNA interaction with (3H)benzo(a)pyrene activated by methylcholanthrene-stimulated microsomes was determined. In agreement with theoretical calculations the inhibitory effectiveness of aminophenols was of the same order of magnitude (between 15-50% protection) as for the phenolic antioxidants. According to our previous findings, this protection is due to the inhibition of cytochrome P-450-dependent microsomal monooxygenases. However, most unexpectedly, it was also found that oxidation products of 4-aminophenol and 4-N-methylaminophenol are significantly more effective than their reduced precursors (protection greater than 95%). The structure of the inhibitory oxidation products of the aminophenols is unknown. However, indirect arguments suggest that some quinoneimines formed as reactive intermediates during the oxidation process could be responsible for this effect. A similar phenomenon was previously found for this effect. A similar phenomenon was previously found for the quinones--diphenols corresponding pairs.
Niculescu-Duvaz
I
I
Institute of Oncology, Bucharest, Romania.
Stoica
G
G
Lupu
F
F
Arnautu
M
M
Voiculetz
N
N
D000627:Aminophenols / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008748:Methylcholanthrene / Q000494:pharmacology; D008861:Microsomes
D000627:Aminophenols; D002273:Carcinogens; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System