GENETIC ANALYSIS OF TK AND HPRT GENE MUTATIONS

我们建议利用细胞遗传学和分子遗传学技术 为了调查在TK发生的诱变事件的频谱 和HPRT基因座在小鼠L5178Y细胞中。这些研究的目的是 是为了确定是否登记了一系列基因异常 在这些基因座上是杂合子/半合子性质的函数 所涉及的基因座位，并将光谱与 已知的发生在人类身上的突变事件。这一频谱，例如 无论是罕见的还是常见的人类癌症，最近 显示的范围从点突变到大片段的丢失 基因组。展示了类似的潜力 在体外试验中登记突变损伤可能会 对了解两国关系有很大帮助 体外诱变潜力与人类遗传病之间的关系。 该项目的第一阶段涉及最近的改编 用于分析的分子类属技术进展 小鼠L5178Y细胞(位于HPRT和TK基因)；第二阶段将 提供半合子HPRT基因的全面分析，以及 TK基因处于杂合子状态。

We propose to utilize cytogenetics and molecular genetic techniques to survey the spectrum of mutageneric events that occur at the TK and HPRT loci in mouse L5178Y cells. The purpose of these studies is to determine if the spectrum of genetic abnormalities registered at these loci is a function of the heterozygous/hemizygous nature of the gene loci involved, and to compare the spectrum with the known mutagenic events that occur in humans. This spectrum, for both rare and frequent forms of human cancer, has recently been shown to range from point mutations to loss of large segments of the genome. The demonstration of a similar potential for registering mutagenic damage in in vitro assays is likely to contribute significantly to the understanding of the relationship between in vitro mutagenic potential and human genetic disease. Phase I of this project dealt with the adaptation of recently devised molecular generic technical developments to analysis of mouse L5178Y cells (at the HPRT and TK genes); Phase II will provide a full scale analysis of the hemizygous HPRT gene, and the TK gene in the heterozygous state.