title: Time-dependent acetylsalicylic acid effects on liver CYP1A and antioxidant enzymes in a rat model of 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinogenesis.
abstract: 7,12-Dimethylbenzanthracene (DMBA) is an abundant environmental contaminant, which undergoes bioactivation, primarily by the CYP1 family, both in liver and extra-hepatic tissues. Dietary acetylsalicylic acid (ASA) has been recently reported to inhibit DMBA-mediated mammary tumour formation in rats. Chemopreventive substances may reduce the risk of developing cancer by decreasing metabolic enzymes responsible for generating reactive species (phase I enzymes) and/or increasing phase II enzymes that can deactivate radicals and electrophiles. To test these hypotheses, Sprague-Dawley female rats were orally administered ASA as lysine acetylsalicylate (50 mg per capita/day for 21 days in water), DMBA (10 mg per capita in olive oil on day 7, 14, and 21), ASA and DMBA in combination, and vehicles only, respectively. Six rats for each group were sacrificed on day 8, 15, and 22. The DMBA-mediated increase in hepatic CYP1A expression and related activities was not significantly affected by ASA, which, conversely, enhanced in a time-dependent manner the liver reduced glutathione content (up to 52%) and the activity of NAD(P)H-quinone oxidoreductase (up to 34%) in DMBA-treated rats. It is proposed that the positive modulation of the hepatic antioxidant systems by ASA may play a role in the chemoprevention of mammary tumourigenesis induced by DMBA in the female rat.
authors.affiliation: Department of Animal Pathology, Division of Pharmacology and Toxicology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Girolami
authors.forename: Giuliana
authors.initials: G
authors.lastname: Abbadessa
authors.forename: Silvia
authors.initials: S
authors.lastname: Racca
authors.forename: Angela
authors.initials: A
authors.lastname: Spaccamiglio
authors.forename: Francesca
authors.initials: F
authors.lastname: Piccione
authors.forename: Mauro
authors.initials: M
authors.lastname: Dacasto
authors.forename: Monica
authors.initials: M
authors.lastname: Carletti
authors.forename: Giulia
authors.initials: G
authors.lastname: Gardini
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Carlo
authors.forename: Carlo
authors.initials: C
authors.lastname: Nebbia
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D001241:Aspirin / Q000097:blood / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000502:physiology*; D019388:Cytochrome P-450 CYP1A2 / Q000502:physiology*; D003580:Cytochromes; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D003580:Cytochromes; D015127:9,10-Dimethyl-1,2-benzanthracene; C017170:Cyp1a2 protein, rat; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D005978:Glutathione; D001241:Aspirin