Interaction of pine cone extract fraction VI with mutagens.
Pine cone extract fraction VI (PC-VI) inhibited the mutagenicity of the promutagens tested: the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) dose-dependently, and the aromatic amines 2-aminoanthracene (AA) and 2-acetylaminofluorene (AAF) at high concentrations. PC-VI had no effect on the mutagenicity of the direct-acting mutagens 2-(2-furyl)-3-(5-nitrofuryl)acrylamide (AF-2) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), but inhibited the mutagenicity of the direct-acting mutagen N-hydroxy 2-acetylaminofluorene (N-OH AAF, proximate mutagen of AAF). The addition of PC-VI to rat hepatic microsomes resulted in a decrease of their enzyme activities, especially NADPH-cytochrome c reductase. By gas-chromatographic analysis of B[a]P or AA contents after incubation of B[a]P or AA and PC-VI and S9 mix, the inhibition of hepatic metabolizing enzymes and the interaction between AA and PC-VI were confirmed. On the other hand, PC-VI had no effect on the DNA repair systems for B[a]P- or AA-induced mutagenesis. We conclude that PC-VI shows indirect antimutagenicity by interfering with cytochrome P-450-dependent bioactivation and by direct interaction with AA and the proximate mutagenic product of AAF.
Lee
H
H
Department of Biochemical Toxicology, School of Medicine, Showa University, Tokyo, Japan.
Aoki
K
K
Sakagami
H
H
Yoshida
T
T
Kuroiwa
Y
Y
D015073:2-Acetylaminofluorene / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D000873:Anthracenes / Q000378:metabolism / Q000633:toxicity; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity; D066298:In Vitro Techniques; D008031:Lignin / Q000494:pharmacology; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000378:metabolism / Q000633:toxicity; D008862:Microsomes, Liver / Q000201:enzymology; D008970:Molecular Weight; D009152:Mutagenicity Tests; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000873:Anthracenes; D016587:Antimutagenic Agents; C069800:PC6 extract; D010936:Plant Extracts; D008769:Methylnitronitrosoguanidine; D001564:Benzo(a)pyrene; C006593:2-anthramine; D008031:Lignin; D015073:2-Acetylaminofluorene