MECHANISMS OF NEOPLASTIC TRANSFORMATION IN CULTURED HUMAN CELLS

过去一年的成就包括以下发现：

Accomplishments of the past year include the following findings: (1) Enhanced chromatid damage in blood lymphocytes after G2 phase x-irradiation can provide a marker for the ataxia telangiectasia (A-T) gene useful for identifying unaffected carriers in A-T families. The persistence of chromatid breaks and gaps, representing unrepaired DNA strand breaks. following radiationinduced DNA damage during G2 phase of the cell cycle suggests deficient DNA repair. This may be the defect at the molecular level that results in the radiosensitivity and cancer-proneness of A-T gene carriers and patients. (2) Lymphoblastoid cell lines can be used in a similar cytogenetic assay to identify in a family with Gardner syndrome (GS) members with the GS gene. (3) Chromosome 11 (ch 11) complements the DNA repair deficiency in six human tumor cell lines. In one line, addition of the long arm of ch 11 was sufficient to restore repair efficiency. These results suggest that ch 11 carries a DNA repair gene. (4) Deficient DNA repair was acquired spontaneously or induced by ras oncogene in diverse lines of human epithelial cells in culture prior to or in association with their neoplastic transformation by virus or chemical carcinogen. (5) 13-cis-- retinoic acid, shown previously to reduce the frequency of skin cancers in xeroderma pigmentosum patients, was found to protect against x-ray-induced chromatid damage in cultured blood lymphocytes. These observations suggest that 13-cis-retinoic acid directly or indirectly acts as a scavenger of the peroxide or (.OH) radicals generated during ionizing radiation, thereby providing protection against x-ray-induced damage.