Mechanisms in Perinatal Carcinogenesis

围产期致癌机制

• 批准号: 6433018
• 负责人: Lucy M Anderson
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6433018
• 关键词: DNA damage; Primates; adduct; aromatic hydrocarbon receptor; chemical carcinogen; chemical carcinogenesis; cis platinum compound; dioxins; drug carcinogenesis; drug related neoplasm /cancer; embryo /fetus drug adverse effect; embryo /fetus toxicology; gene mutation; genetic strain; halobiphenyl /halotriphenyl compound; laboratory mouse; liver neoplasms; pediatric neoplasm /cancer; perinatal; placental transfer; tamoxifen; tumor promoters; zidovudine

Perinatal exposures may lead to increased risk of childhood cancers, as well as those later in life. Preconceptional parental, transplacental, and/or neonatal exposures may be involved. Studies with animal models are utilized to increase understanding of underlying cellular and molecular mechanisms. Transmammary neonatal exposures have received relatively little attention. We have studied exposure by this route to the carcinogenic nitrosamine, N-nitrosodimethylamine, which is present in tobacco smoke and other environmental sources. After administration to lactating rat mothers, N-nitrosodimethylamine caused formation in tissues of suckling infants of a DNA adduct known to be associated with tumor initiation. Furthermore, if the mother received ethanol at the same time, there was a 10-fold increase in these adducts in some tissues. These results indicate that transmammary exposures should receive further study. Another understudied exposure issue is that of transgenerational carcinogenesis. We are examining the effects of paternal exposure to chromium(III), a chemical widely encountered occupationally. Exposure of male mice to this chemical before mating leads to increased incidence of several types of neoplasms in the offspring. Preliminary results indicate that this is associated with changes in serum hormones in the offspring, and altered expression of a number of hepatic genes as studied by microarray, including insulin-like growth factor binding protein 1. AIDS Title:

围产期接触可能会导致儿童期以及晚年罹患癌症的风险增加。可能涉及孕前父母、经胎盘和/或新生儿的暴露。利用动物模型研究来增进对潜在细胞和分子机制的理解。经乳房新生儿暴露受到的关注相对较少。 我们研究了通过这种途径接触致癌亚硝胺、N-亚硝基二甲胺的情况，这种物质存在于烟草烟雾和其他环境来源中。 给予哺乳期大鼠母亲后，N-亚硝基二甲胺导致乳婴组织中形成已知与肿瘤发生相关的 DNA 加合物。 此外，如果母亲同时接受乙醇，某些组织中这些加合物的含量会增加 10 倍。这些结果表明经乳房暴露应接受进一步研究。另一个未充分研究的暴露问题是跨代致癌。 我们正在研究父亲接触铬（III）的影响，铬（III）是一种在职业中广泛遇到的化学物质。 雄性小鼠在交配前接触这种化学物质会导致后代几种肿瘤的发病率增加。 初步结果表明，这与后代血清激素的变化以及通过微阵列研究的许多肝脏基因的表达改变有关，包括胰岛素样生长因子结合蛋白1。 艾滋病标题：