Amacher D E, Zelljadt I
Mutat Res. 1984 May;136(2):137-45. doi: 10.1016/0165-1218(84)90156-3.
4 presumptive clastogens (caffeine, dimethyl sulfoxide, diethylstilbestrol and p,p'-DDE) and 4 chemicals thought to induce chromosomal mutations in L5178Y mouse lymphoma cells (procarbazine X HCl, epichlorohydrin, hycanthone and iodomethane) were tested in the CHO/HGPRT gene mutation assay for the induction of 6-thioguanine-resistant ( 6TGR ) mutants. Of the clastogens, p,p'-DDE was mutagenic at several concentrations and diethylstilbestrol (DES) increased the 6TGR mutant frequency over control levels at the 6.7 and 8.0 micrograms/ml doses, but the results for DES were neither convincing nor significant. Caffeine was not mutagenic although at very high concentrations (6667-8000 micrograms/ml) there was a slight elevation in mutant frequency over background. This was probably due to a selective effect of caffeine against the HGPRT+ phenotype, for 2 different HGPRT- cell lines were refractory to the toxic effects of caffeine at the highest test level (8000 micrograms/ml). All 4 'chromosomal mutagens' produced dose-related increases in mutant frequencies at the HGPRT locus of these CHO cells. 6TGR colonies were generally uniform in size when normal precautions were taken to prevent the formation of satellite (secondary) colonies. Excepting DES, dimethyl sulfoxide, and caffeine, these data demonstrate that 5 of 8 clastogenic chemicals reproducibly induce mutations at the HGPRT locus of CHO cells which lack the small colony-forming potential of 3.7.2C L5178Y cells.
在CHO/HGPRT基因突变试验中,对4种推定的致断裂剂(咖啡因、二甲基亚砜、己烯雌酚和p,p'-滴滴涕)以及4种被认为可在L5178Y小鼠淋巴瘤细胞中诱导染色体突变的化学物质(盐酸甲基苄肼、环氧氯丙烷、海恩酮和碘甲烷)进行了测试,以检测其诱导6-硫鸟嘌呤抗性(6TGR)突变体的能力。在这些致断裂剂中,p,p'-滴滴涕在几个浓度下具有致突变性,己烯雌酚(DES)在6.7和8.0微克/毫升剂量下使6TGR突变体频率高于对照水平,但DES的结果既不令人信服也不显著。咖啡因没有致突变性,尽管在非常高的浓度(6667 - 8000微克/毫升)下,突变体频率比背景略有升高。这可能是由于咖啡因对HGPRT+表型的选择性作用,因为2种不同的HGPRT-细胞系在最高测试水平(8000微克/毫升)下对咖啡因的毒性作用具有抗性。所有4种“染色体诱变剂”在这些CHO细胞的HGPRT位点均产生了与剂量相关的突变体频率增加。当采取正常预防措施防止卫星(次级)菌落形成时,6TGR菌落的大小通常是均匀的。除了DES、二甲基亚砜和咖啡因外,这些数据表明,8种致断裂化学物质中的5种可在缺乏3.7.2C L5178Y细胞小菌落形成潜力的CHO细胞的HGPRT位点可重复性地诱导突变。