MECHANISMS OF NEOPLASTIC TRANSFORMATION IN CULTURED HUMAN CELLS

过去一年取得的成就包括以下调查结果： (1)G2期后血淋巴细胞染色单体损伤增强 X线照射可作为共济失调毛细血管扩张症（A-T）的标志物 用于鉴定A-T家族中未受影响的携带者的基因。 的 染色单体断裂和间隙的持续存在，代表未修复的DNA 链断裂。在G2期辐射诱导的DNA损伤后， 细胞周期表明DNA修复缺陷 这可能是缺陷， 导致放射敏感性的分子水平， A-T基因携带者和患者的癌症倾向。(2)淋巴母 细胞系可用于类似的细胞遗传学测定中， 加德纳综合征（GS）家族成员具有GS基因。（三） 11号染色体（ch 11）补充了6名人类的DNA修复缺陷 肿瘤细胞系 在一条线中，增加了CH 11的长臂， 足以恢复修复效率。 这些结果表明，CH 11携带DNA修复基因。(4)DNA修复缺陷 在不同的人类品系中自发或由ras癌基因诱导 上皮细胞在培养之前或与它们的 由病毒或化学致癌物引起的肿瘤转化。(5)13-顺式 视黄酸，以前被证明可以降低皮肤癌的发生率 在着色性干皮病患者中， x射线诱导的培养血淋巴细胞染色单体损伤。 这些 观察表明，13-顺式维甲酸直接或间接 作为过氧化物或（.OH）自由基的清除剂， 电离辐射，从而提供对X射线诱导的 损害

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.