TUMORIGENICITY OF THE TOBACCO-SPECIFIC CARCINOGEN 4-(METHYL-NITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE IN INFANT MICE
TUMORIGENICITY OF THE TOBACCO-SPECIFIC CARCINOGEN 4-(METHYL-NITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE IN INFANT MICE
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DOI：
10.1016/0304-3835(91)90097-2
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发表时间：
1991-07-04
期刊：
影响因子：
9.7
通讯作者：
RICE, JM
中科院分区：
文献类型：
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作者：
ANDERSON, LM;HECHT, SS;RICE, JM
烟草特有的亚硝胺，4-（甲基-亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK），是成年啮齿类动物中的一种强致癌物，并且根据物种的不同，具有经胎盘的毒性作用。 为了追求人类婴儿可能是烟草烟雾成分引发肿瘤的特别脆弱的靶标这一论点，我们测试了NNK作为婴儿小鼠中肿瘤引发剂的功效。 在出生后第1、4、7、10和14天，对Cr：NIH（S）（NIH Swiss远系杂交）小鼠腹膜内给予50 mg/kg NNK，对照组给予生理盐水。 在平均年龄为13-15个月时，57%的NNK暴露的雄性后代患有肝细胞肿瘤，多重性为1.15 +/- 1.4，包括4例癌。 在8只（14%）暴露于NNK的雌性后代中发现肝肿瘤，包括2例癌。 在任何对照组中均无肝细胞肿瘤。 原发性肺肿瘤的显著增加也发生在NNK治疗的雄性动物中，发生率为30/55（57%），多重性为0.7 +/- 0.2，而对照组为7/33（21%），多重性为0.3 +/- 0.6（P < 0.025）。 NNK处理的雌性中肺肿瘤的发生率明显增加，21/57（37%）对比对照中的7/32（22%），接近显著性（P < 0.1）。 因此，NNK是瑞士幼鼠肝脏和肺的中等强效新生儿致癌物，在这方面比相同品系小鼠经胎盘接受时更有效。
The tobacco-specific nitrosamine, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a potent carcinogen in adult rodents and variably effective transplacentally, depending on species. In pursuit of the thesis that human infants may be especially vulnerable targets for tumor initiation by tobacco smoke constituents, we tested the efficacy of NNK as a tumor initiator in infant mice. Cr:NIH(S) (NIH Swiss outbred) mice were given 50 mg/kg NNK i.p. on postnatal days 1, 4, 7, 10 and 14, with saline to controls. At an average age of 13-15 months, 57% of the NNK-exposed male off-spring had hepatocellular tumors, with a multiplicity of 1.15 +/- 1.4, including 4 with carcinoma. Liver tumors including 2 carcinomas were found in 8 (14%) of the NNK-exposed female offspring. There were no hepatocellular neoplasms in any control. A significant increase in primary lung tumors also occurred in the NNK-treated males, with an incidence of 30/55 (57%) and a multiplicity of 0.7 +/- 0.2, vs. 7/33 (21%), multiplicity 0.3 +/- 0.6, in controls (P < 0.025). An apparent increase in the incidence of lung tumors in NNK-treated females, 21/57 (37%) vs. 7/32 (22%) in controls, approached significance (P < 0.1). Thus NNK was a moderately potent neonatal carcinogen for liver and lung in infant Swiss mice and more efficacious in this regard than when received transplacentally by mice of the same strain.