Okinaka R T, Whaley T W, Strniste G F
Life Sciences Division, Los Alamos National Laboratory, NM 87545.
Mutat Res. 1988 Sep-Oct;209(1-2):45-50. doi: 10.1016/0165-7992(88)90109-1.
The direct-acting cytotoxic properties of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxy-2-aminofluorene (N-OH-AF) have been determined in repair-proficient (AA8-4) and repair-deficient (UV-5) Chinese hamster ovary cells. Cytotoxicity comparisons indicate that UV-5 cells are considerably more sensitive to exposure to N-OH-AAF than is the parental AA8-4 cell line, i.e., concentrations needed to obtain a D37 for survival of AA8-4 is greater than 5-fold higher than for UV-5. Mutation analysis at the HGPRT locus also indicates the increased sensitivity of UV-5 cells to N-OH-AAF as witnessed by an enhanced induction of 6-thioguanine-resistant colonies at equitoxic doses. Conversely, N-OH-AAF, did not induce a 'UV-mimetic' response when comparing genotoxicity between these two cell lines. Our data coupled with previously published model-building and adduct removal studies (Broyde and Hingerty, 1983; Fuchs and Daune, 1974; Grunberger and Weinstein, 1976; Yamasaki et al., 1977) suggest that the minor DNA adduct species, N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene, may be responsible for the hypermutagenicity witnessed in DNA excision-repair-deficient cells treated with N-OH-AAF.
已在修复功能正常的（AA8 - 4）和修复功能缺陷的（UV - 5）中国仓鼠卵巢细胞中测定了N - 羟基 - 2 - 乙酰氨基芴（N - OH - AAF）和N - 羟基 - 2 - 氨基芴（N - OH - AF）的直接细胞毒性特性。细胞毒性比较表明，UV - 5细胞对暴露于N - OH - AAF的敏感性比亲本AA8 - 4细胞系高得多，即获得AA8 - 4细胞存活的D37所需的浓度比UV - 5细胞高5倍以上。在次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HGPRT）位点的突变分析也表明，在等毒性剂量下，UV - 5细胞对N - OH - AAF的敏感性增加，表现为6 - 硫鸟嘌呤抗性集落的诱导增强。相反，在比较这两种细胞系之间的遗传毒性时，N - OH - AAF未诱导出“UV模拟”反应。我们的数据与先前发表的模型构建和加合物去除研究（Broyde和Hingerty，1983；Fuchs和Daune，1974；Grunberger和Weinstein，1976；Yamasaki等人，1977）表明，次要的DNA加合物种类N - （2'-脱氧鸟苷 - 8 - 基）-2 - 乙酰氨基芴可能是在用N - OH - AAF处理的DNA切除修复缺陷细胞中所见的高致突变性的原因。
