Carcinogen specificity in the activation of transforming genes by direct-acting alkylating agents.
Carcinogen specificity in the activation of transforming genes by direct-acting alkylating agents.
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直接作用烷化剂激活转化基因的致癌特异性。
DOI：
10.1093/carcin/6.12.1709
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发表时间：
1985
期刊：
影响因子：
4.7
通讯作者：
Albert,RE
中科院分区：
文献类型：
--
作者：
Garte,SJ;Hood,AT;Hochwalt,AE;D'Eustachio,P;Snyder,CA;Segal,A;Albert,RE
用DNA转染法检测了烷化剂甲基甲烷磺酸盐（MMS）、β-丙内酯（BPL）和二甲基氨基甲酰氯（DMCC）诱导的大鼠鼻和小鼠皮肤癌和纤维肉瘤的DNAs转化NIH 3 T3细胞的能力。8例MMS诱导的大鼠鼻癌和2例BPL诱导的小鼠皮肤肿瘤在转染试验中均为阳性，而DMCC诱导的4例纤维肉瘤和6例癌均为阴性。锚定非依赖性生长、裸鼠致瘤性和二次转染证实了阳性转染子的转化表型。从MMS诱导的肿瘤DNA的转染子不包含限制性片段同源的大鼠H-，K-或N-ras癌基因，虽然外源性（大鼠）肿瘤衍生的DNA序列中检测到转染基因组Southern分析。相反，BPL诱导的小鼠皮肤肿瘤显示出含有活化的H-ras的证据。这些结果表明，在实验性肿瘤中，致癌物对转化基因的激活具有特异性。
DNAs from rat nasal and mouse skin carcinomas and fibrosarcomas induced by the alkylating agents methylmethane sulfonate (MMS), β-propiolactone (BPL), and dimethyl-carbamyl chloride (DMCC) were tested for their ability to transform NIH3T3 cells by DNA transfection. Each of eight MMS-induced rat nasal carcinomas and two of five BPL-induced mouse skin tumors were positive in the transfection assay while all of four fibrosarcomas and six carcinomas induced by DMCC were negative. Anchorage independent growth, tumorigenicity in nude mice, and secondary transfection confirmed the transformed phenotype of the positive transfectants. The transfectants from MMS-induced tumor DNAs did not contain restriction fragments homologous to rat H-, K- or N-ras oncogenes although exogenous (rat) tumor-derived DNA sequences were detected in transfectant genomes by Southern analysis. In contrast a BPL-induced mouse skin tumor showed evidence of containing activated H-ras. These results suggest specificity among causal carcinogens for activation of transforming genes in experimental tumors.