DIET CANCER AND ONCOGENE EXPRESSION IN INBRED MICE

近交小鼠的饮食癌和癌基因表达

• 批准号: 3191332
• 负责人: ELSIE WAINFAN
• 金额: $ 7.9万
• 依托单位: NEW YORK BLOOD CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3191332
• 关键词: 5 methylcytosine; DNA methylation; Retroviridae; chemical carcinogenesis; choline; cysteine; cytosine; dietary supplements; endonuclease; gene expression; genetic strain; hepatocellular carcinoma; inbreeding; messenger RNA; methionine; molecular oncology; mouse leukemia; neoplasm /cancer genetics; nucleic acid hybridization; nucleic acid sequence; nutrition aspect of cancer; nutrition related neoplasm /cancer; nutrition related tag; oncogenes; tumor promoters; vitamin B12 coenzyme

The goals of this research are: 1. to determine whether dietary levels of lipotropes (methionine, choline, folic acid, and Vitamin B12) can influence the time of onset and/or severity of tumors in inbred mice of strains that have a high spontaneous incidence of leukemia or hepatomas; 2. to determine what effect the dietary level of lipotropes has on methylation of DNA (overall and of several specific genes); and 3. to determine whether the level of dietary lipotropes affects time and quantity of oncogene expression. Mice of the strains AKR/J, C3H/HeJ, B6C3F1/J and C57BL/6J will be fed semipurified diets that are either deficient, adequate, or enriched with lipotropes. After receiving one of the diets listed above for periods ranging from one week to three months, the animals will be sacrificed and RNA and DNA will be isolated from their excised tissues. Extent of hypomethylation of DNA will be assayed by measuring the ability of DNA to accept methyl groups in vitro in assays with homologous enzymes, by determining the ratio of 5-methylcytosine to cytosine of the DNA, and by determining the susceptibility of genomic DNA to cleavage by restriction endonucleases, whose action is sensitive to the presence of 5-methylcytosine or cytsine residues in their recognition/cleavage sites. We will study the restriction endonuclease digestion patterns of c-myc, c-Ha -ras, c-Ki-ras and several other oncogenes. We will utilize DNA:RNA hybridization techniques to determine the levels of mRNA for these oncogenes. Long term feeding of the diets of differing lipotrope content will be carried out to see whether this results in alterations in the time of spontaneous onset or number and severity of hepatic tumors in C3H and B6C3F1 mice, and the time of on set and severity of leukemia in ARK mice. C57BL/6 mice, which have low spontaneous cancer incidence will be used as controls. It is known that lipotrope-deficient diets promote chemical carcinogenesis in rodents, and that diets supplemented with methionine and choline can cause a decreased response to some carcinogens, but it is not known whether supplements of methionine and choline can suppress or whether lipotrope deficiency can accelerate the development of cancer in animals with an inherited high frequency of neoplasia.

本研究的目的是：1.以确定饮食是否 抗脂蛋白（蛋氨酸、胆碱、叶酸和维生素 B12）可以影响肿瘤的发作时间和/或严重程度， 具有高自发发病率的品系的近交系小鼠 白血病或肝癌; 2.来确定饮食对 水平对DNA甲基化（总体和 几个特定基因）;和3.以确定是否 饮食促脂蛋白影响癌基因表达的时间和数量 表情 AKR/J、C3H/HeJ、B6C3F1/J和 C57 BL/6 J将饲喂半纯化饲料，这些饲料要么缺乏， 足够的，或富含抗脂蛋白。 在收到一份 以上列出的饮食，从一周到三周不等 几个月后，动物将被处死， 从他们的切除组织中分离出来。 低甲基化程度 DNA将通过测量DNA接受 甲基基团在体外测定同源酶，通过 测定5-甲基胞嘧啶与胞嘧啶的比率， DNA，并通过确定基因组DNA的易感性， 通过限制性内切核酸酶切割，其作用对 5-甲基胞嘧啶或胞嘧啶残基在其 识别/切割位点。 我们将研究限制 c-myc、c-Ha -ras、c-Ki-ras和 其他几种致癌基因。 我们将利用DNA：RNA杂交 技术来确定这些致癌基因的mRNA水平。 长期饲喂不同促脂素含量的日粮， 进行，看看这是否会导致改变， 自发发作的时间或肝硬化的数量和严重程度 C3 H和B6 C3 F1小鼠中的肿瘤，以及开始和 方舟小鼠白血病的严重程度。 C57 BL/6小鼠， 低自发性癌症发病率将用作对照。 是 已知缺乏促脂素饮食促进化学物质 致癌作用，饮食中补充 甲硫氨酸和胆碱会导致对一些 致癌物，但尚不清楚补充剂是否 甲硫氨酸和胆碱可以抑制或 缺乏可加速动物癌症的发展 遗传性高频率的肿瘤