Chemopreventive potential of fumaric acid, N-acetylcysteine, N-(4-hydroxyphenyl) retinamide and β-carotene for tobacco-nitrosamine-induced lung tumors in A/J mice

被引:24
作者
Conaway, CC
Jiao, D
Kelloff, GJ
Steele, VE
Rivenson, A
Chung, FL
机构
[1] Amer Hlth Fdn, Div Carcinogenesis & Mol Epidemiol, Valhalla, NY 10595 USA
[2] Nabisco Inc, E Hanover, NJ 07936 USA
[3] NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA
关键词
chemopreventive agent; fumaric acid; N-acetylcysteine; N-(4-hydroxyphenyl) retinamide; beta-carotene; 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone; lung tumors; strain A/J mice;
D O I
10.1016/S0304-3835(97)00454-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Four agents, fumaric acid (FA), N-acetylcysteine (NAG), N-(4-hydroxyphenyl) retinamide (4-HPR) and beta-carotene (beta-CT), were evaluated for potential chemopreventive activity using the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor model in female A/J mice. The agents were evaluated in both 16-week and 52-week bioassays at two dose levels corresponding to 0.8 maximum tolerated dose (MTD) and 0.4 MTD administered throughout the bioassay either in the diet (FA, 160 and 80 mmol/kg diet; NAG, 160 and 80 mmol/kg diet; 4-HPR, 4 and 2 mmol/kg diet) or by subcutaneous injection twice a week (beta-CT, 32 and 16 mg/kg b.w.). Mice were treated with a single i.p. dose of 10 mu mol NNK in saline 1 week after administration of test agent. Lung adenomas were evaluated in the 16-week bioassay, whereas both adenomas and adenocarcinomas of the lung were determined in the 52-week bioassay. Both bioassays showed that all four agents did not significantly inhibit the total tumor incidence and multiplicity of the lung. However, the incidence of adenocarcinomas was reduced (P < 0.01) at 52 weeks in NNK groups given either 0.8 MTD NAC or 0.8 MTD beta-CT compared with the NNK control group. The decreases in adenocarcinomas were accompanied by corresponding increases in adenomas in these treatment groups. Thus, this study showed that FA, NAG, 4-HPR and beta-CT did not inhibit the total tumor formation, however, at the higher doses both NAC and beta-CT significantly retarded the malignant progression in the lung of NNK-treated A/J mice. Published by Elsevier Science Ireland Ltd.
引用
收藏
页码:85 / 93
页数:9
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