Odeleye O E, Eskelson C D, Mufti S I, Watson R R
Department of Family and Community Medicine, Arizona Health Sciences Center, University of Arizona, Tucson 85724.
Carcinogenesis. 1992 Oct;13(10):1811-6. doi: 10.1093/carcin/13.10.1811.
Retrovirally induced immunosuppression may elevate the incidence of chemically induced cancers. A proposed hypothesis to explain this relationship is the increased free radical activity observed during retroviral infection and carcinogen activation. We previously found that vitamin E retarded growth of esophageal tumors accompanied by reductions of free radical products. This study investigated the contribution that retroviral immunosuppression has on esophageal cancer induced by the carcinogen N-nitrosomethylbenzylamine (NMBzA), and the response that increased levels of dietary vitamin E has on this induced carcinogenesis. Female C57BL/6 mice received NMBzA or vehicle (corn oil) i.p. weekly for 3 weeks. Then some of the mice were infected with LP-BM5 murine retrovirus and fed diets containing 30 IU vitamin E or 172 IU vitamin E/kg of diet. As an assessment of free radical activity, exhaled ethane was measured prior to killing the animals at 26 weeks. Esophagi from the various mice groups were assessed for size and frequency of tumors. Livers homogenates were analyzed for vitamins A and E, lipid fluorescence, conjugated dienes and malondialdehyde. Hepatic levels of vitamin A and E were decreased (P < 0.05) and indices of lipid peroxidation were greater (P < 0.05) in NMBzA-treated mice relative to controls. Lipid peroxidation and serum transaminases (ALT and AST) were greatest in mice given NMBzA and infected with the retroviruses. Incidence of esophageal tumors were also greatest in the NMBzA-treated, immunocompromised animals. Mice fed vitamin E-supplemented diets showed increased (P < 0.05) hepatic concentrations of vitamin E and vitamin A, decreased activities of serum transaminases, decreased indices of lipid peroxidation, and decreased size and frequency of esophageal tumors in both the immunocompromised and non-immunocompromised mice. These results suggest that vitamin E plays an antioxidant function that retards the incidence of esophageal cancers in immunocompromised and non-immunocompromised animals.
逆转录病毒诱导的免疫抑制可能会提高化学诱导癌症的发病率。一个用来解释这种关系的假说认为，在逆转录病毒感染和致癌物激活过程中会观察到自由基活性增加。我们之前发现维生素E可抑制食管肿瘤生长，并伴有自由基产物减少。本研究调查了逆转录病毒免疫抑制对致癌物N-亚硝基甲基苄胺（NMBzA）诱导的食管癌的影响，以及膳食中维生素E水平升高对这种诱导性致癌作用的反应。雌性C57BL/6小鼠每周腹腔注射一次NMBzA或赋形剂（玉米油），持续3周。然后，部分小鼠感染LP-BM5鼠逆转录病毒，并喂食含30 IU维生素E或172 IU维生素E/千克饲料的日粮。作为对自由基活性的评估，在26周处死动物前测量呼出的乙烷。评估不同小鼠组食管的肿瘤大小和发生率。分析肝脏匀浆中的维生素A和E、脂质荧光、共轭二烯和丙二醛。与对照组相比，NMBzA处理的小鼠肝脏中维生素A和E水平降低（P<0.05），脂质过氧化指标更高（P<0.05）。在给予NMBzA并感染逆转录病毒的小鼠中，脂质过氧化和血清转氨酶（ALT和AST）水平最高。在接受NMBzA处理的免疫受损动物中，食管肿瘤的发生率也最高。喂食补充维生素E日粮的小鼠，无论是免疫受损还是未免疫受损的小鼠，其肝脏中维生素E和维生素A浓度均升高（P<0.05），血清转氨酶活性降低，脂质过氧化指标降低，食管肿瘤的大小和发生率降低。这些结果表明，维生素E发挥抗氧化功能，可降低免疫受损和未免疫受损动物食管癌的发生率。
