Biochemical changes in α-naphthyl isothiocyanate-induced chronic cholangitis in the rat

Nikolaev, V. B.; Kerimova, M.; Naydenova, E.; Ivanov, E; Dontchev, N; Adjarov, D

doi:10.1016/s0232-1513(88)80083-5

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(2 citation statements)

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“…In our study, ANIT elevated the activities of phase II enzymes, GST and QR in the liver. ANIT has been reported to increase the activity of GST,20 which can inhibit DNA binding of N ‐acetyl‐PhIP in vitro 28. Thus, increased activities of GST and QR, particularly GST, in the liver may be one of the major causes of its cancer‐suppressing effect observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms of its chemopreventive effect have been discussed;18 one possible mechanism is the regulation of phase I and phase II enzymes. ANIT has been shown to decrease hepatic cytochrome P‐450 content,19, 20 and hepatic mixed‐function oxidase activities,21 and increase microsomal epoxide hydrolase and cytosolic DT‐diaphorase activities 19. The promutagenic PhIP found in cooked foods is converted to the active form mainly by cytochromes P450 1A1, 1A2 and 1B1 in the liver and partially in the target organs 21, 22, 23, 24, 25, 26, 27.…”

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confidence: 99%

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Effect of α‐naphthyl isothiocyanate on 2‐amino‐3‐methylimidazo[4,5‐b]pyridine (PhIP)‐induced mammary carcinogenesis in rats

Sugie

Ohnishi

Ushida

et al. 2005

Intl Journal of Cancer

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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.

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Section: Discussionmentioning

confidence: 99%