Effect of alpha-naphthyl isothiocyanate on 2-amino-3-methylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in rats.
The modifying effects of alpha-naphthyl isothiocyanate (ANIT) on 2-amino-3-methylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis were investigated in female Sprague-Dawley (SD) rats, and the hepatic activities of the phase II detoxifying enzymes glutathione S-transferase (GST) and quinone reductase (QR) were also assayed. Ninety-eight rats were divided into 4 groups. Starting at 6 weeks of age, rats were fed the high-fat diet without ANIT (Groups 1 and 4) or the experimental diet (high-fat diet mixed with 400 ppm ANIT, Groups 2 and 3). At 7 weeks of age, Groups 1 and 2 were given PhIP in corn oil (85 mg/kg body weight, 8 times for 11 days) by intragastric intubation. One week after the last PhIP injection, 5 rats in each group were sacrificed to assay GST and QR activities, and the experimental diets for Groups 2 and 3 were switched to the high-fat diet without ANIT until termination of the experiment. Group 4 served as the vehicle control. All rats were sacrificed at 24 weeks after the start of the experiment. At termination of the experiment, mammary tumours were detected in Groups 1 (PhIP alone) and 2 (PhIP + ANIT) and were shown histologically to be adenocarcinomas; their incidences (multiplicities) were 56.3% (1.66 +/- 2.31/rat) in Group 1 and 6.7% (0.07 +/- 0.25/rat) in Group 2 (p < 0.001). Mean sizes of the tumours were 10.6 +/- 5.3 mm in Group 1 and 6.5 mm in Group 2. No mammary tumours were observed in rats of Groups 3 and 4. In addition, ANIT treatment significantly increased the activities of GST and QR in the livers of rats in Groups 2 and 3 as compared to Groups 1 and 4. These results imply that the isothiocyanate compound ANIT shows potent inhibitory effects on mammary carcinogenesis induced by PhIP in female SD rats when administered during the initiation stage.
Sugie
Shigeyuki
S
Department of Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. sugie@kanazawa-med.ac.jp <sugie@kanazawa-med.ac.jp>
Ohnishi
Masami
M
Ushida
Jun
J
Yamamoto
Tomohiro
T
Hara
Akira
A
Koide
Akihiro
A
Mori
Yukio
Y
Kohno
Hiroyuki
H
Suzuki
Rikako
R
Tanaka
Takuji
T
Wakabayashi
Keiji
K
Mori
Hideki
H
D015058:1-Naphthylisothiocyanate / Q000627:therapeutic use*; D000230:Adenocarcinoma / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004032:Diet; D004359:Drug Therapy, Combination; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D007093:Imidazoles / Q000633:toxicity*; 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
D002273:Carcinogens; D007093:Imidazoles; D015058:1-Naphthylisothiocyanate; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase