Cho Y S, Kim K B, Chung A S
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejeon, South Korea.
Mutat Res. 1998 Feb 2;397(2):263-9. doi: 10.1016/s0027-5107(97)00224-8.
6-Sulfooxymethylbenzo[a]pyrene (SMBP) is an ultimate and reactive form of 6-hydroxymethybenzo[a]pyrene (HMBP), which is converted into SMBP by the mediation of sulfotransferase. SMBP and HMBP with metabolic activation were mutagenic to S. typhimurium TA98 and TA100. The number of mutation per plate in strain TA98 was proportional to the concentrations of SMBP ranging from 0.2 to 1.0 nmol/plate, whereas that in strain TA100 was decreased at concentrations above 0.6 nmol/plate. The mutation frequencies by HMBP was also increased in a dose dependent manner in both strains. Furthermore, SMBP and HMBP were highly mutagenic and cytotoxic to Chinese hamster lung fibroblast (V79) cells. A dose-dependent increase in mutation frequencies at both hypoxanthine:guanine phosphoribosyltransferase (HGPRT) and sodium/potassium-ATPase (Na/K-ATPase) loci were found in V79 cells treated with SMBP and HMBP. The cytotoxicity of SMBP was increased with the increasing concentrations up to 2.5 microM, where the survival frequency and growth rate were decreased to almost 40% and 30% of the control value, respectively. The survival frequencies of V79 cells by HMBP were also decreased in a dose dependent manner up to 180 microM as similar to those of SMBP but the effects were less remarkable. SMBP was progressively accumulated in V79 cells, reaching plateau in just 30 min. A dose dependent increase in complex formation with DNA or proteins was observed by treatment with SMBP. The mutagenicity and cytotoxicity of SMBP and HMBP may be derived from their binding capacity to DNA in V79 cells and S. typhimurium.
6-磺氧基甲基苯并[a]芘(SMBP)是6-羟甲基苯并[a]芘(HMBP)的一种终末反应形式,它通过磺基转移酶的介导由HMBP转化而来。经代谢活化的SMBP和HMBP对鼠伤寒沙门氏菌TA98和TA100具有致突变性。TA98菌株中每平板的突变数与SMBP浓度(范围为0.2至1.0 nmol/平板)成正比,而TA100菌株中当浓度高于0.6 nmol/平板时突变数减少。两种菌株中HMBP的突变频率也呈剂量依赖性增加。此外,SMBP和HMBP对中国仓鼠肺成纤维细胞(V79)具有高度致突变性和细胞毒性。在用SMBP和HMBP处理的V79细胞中,次黄嘌呤:鸟嘌呤磷酸核糖转移酶(HGPRT)和钠/钾-ATP酶(Na/K-ATP酶)位点的突变频率均呈剂量依赖性增加。SMBP的细胞毒性随着浓度增加至2.5 microM而增强,此时存活频率和生长速率分别降至对照值的近40%和30%。与SMBP类似,HMBP处理的V79细胞存活频率也呈剂量依赖性降低,直至180 microM,但效果不太显著。SMBP在V79细胞中逐渐积累,仅30分钟就达到平台期。用SMBP处理后观察到与DNA或蛋白质形成复合物的剂量依赖性增加。SMBP和HMBP的致突变性和细胞毒性可能源于它们与V79细胞和鼠伤寒沙门氏菌中DNA的结合能力。