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:

围产期暴露可能会导致儿童癌症以及以后生活的风险增加。可能会涉及预感的父母，移植和/或新生儿暴露。使用动物模型的研究用于增加对潜在的细胞和分子机制的理解。跨乳腺新生儿暴露的关注相对较少。 我们已经通过这种途径研究了接触致癌的亚硝基胺，N-硝基二甲胺，该胺存在于烟草烟雾和其他环境来源中。 给予泌乳大鼠母亲后，N-亚硝基二甲胺会导致已知与肿瘤启动有关的DNA加合物的哺乳婴儿的组织形成。 此外，如果母亲同时接受乙醇，则某些组织中这些加合物的增加了10倍。这些结果表明，跨乳房暴露应接受进一步的研究。另一个研究的暴露问题是转世癌发生。 我们正在研究父亲暴露于铬（III）的影响，这是一种广泛遇到职业的化学物质。 在交配之前，雄性小鼠接触这种化学物质会导致后代中几种类型的肿瘤的发生率增加。 初步结果表明，这与MicroArray所研究的许多肝基因的表达以及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。IADS标题：