Protective effect of dimethyl-4,4'-dimethoxy-5,6,5', 6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) against carcinogen-induced rat liver nuclear DNA damage.
The protective effect of DDB against carcinogen-induced DNA damage was examined in the present investigation. Preincubation of rat liver nuclei with DDB (1 mmol.L-1) resulted in 60% inhibition of binding of 3H-benzo(a)pyrene to nuclear DNA. Unscheduled DNA synthesis (UDS) induced by aflatoxin B1 (10(-7) mol.L-1) in freshly isolated rat hepatocytes was also inhibited by DDB (10(-6)-10(-3) mol.L-1). Oral administration of DDB at 200 mg.kg-1 once daily for 3 d induced a significant increase of liver cytosol glutathione-S-transferase and microsomal UDPG-transferase activity in mice. These results indicate that DDB is able to directly or indirectly antagonize certain carcinogen-induced DNA damages.
Qing
W
W
Department of Pharmacology, Chinese Academy of Medical Sciences, Beijing.
Liu
G
G
D000818:Animals; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004149:Dioxoles / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004149:Dioxoles; D001564:Benzo(a)pyrene; C041398:7,7'-dimethoxy-(4,4'-bi-1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase