Arranz N, Haza A I, García A, Möller L, Rafter J, Morales P
Departamento de Nutrición, Bromatología y Tecnología de los Alimentos, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Food Chem Toxicol. 2007 Sep;45(9):1662-9. doi: 10.1016/j.fct.2007.02.032. Epub 2007 Mar 12.
The aim of this study was to investigate the protective effect of organosulfur compounds towards N-nitrosamine-induced DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay. N-Nitrosopyrrolidine (NPYR) and N-nitrosodimethylamine (NDMA) incubated with formamidopyrimidine-DNA glycosylase (Fpg), caused a significant increase in oxidative DNA damage in comparison to the solvent control, the lowest effective concentrations, being 5 and 27 mM, respectively. NPYR exerted greater genotoxic effects than NDMA. None of the organosulfur compounds (OSCs) concentrations tested in presence or absence of Fpg enzyme, caused DNA damage per se. OSCs (diallyl sulfide, DAS and dipropyl sulfide, DPS, 1-50 microM; diallyl disulfide, DADS and dipropyl disulfide, DPDS, 1-5 microM) reduced the genotoxic effects of the N-nitrosamines in a dose-dependent manner when HepG2 cells were simultaneously treated with OSCs and N-nitrosamines. The effect of NPYR was attenuated by about 61-67%, respectively, with the highest concentration of DAS (50 microM) and DADS (5 microM). The protective effect of DADS (5 microM, 66%) was higher than DAS (50 microM, 53%) towards NDMA-induced oxidative DNA damage. A concentration of 50 microM DPS and 5 microM DPDS led to a 65-63% and 59-65% reduction in NPYR/NDMA-induced oxidative DNA damage, respectively. Our results indicate that OSCs protect human-derived cells against the oxidative DNA damaging effect of NPYR and NDMA, two carcinogenic compounds which occur in the environment.
本研究的目的是在单细胞凝胶电泳(SCGE)/HepG2检测中,研究有机硫化合物对N-亚硝胺诱导的DNA损伤的保护作用。与溶剂对照相比,用甲酰胺嘧啶-DNA糖基化酶(Fpg)孵育的N-亚硝基吡咯烷(NPYR)和N-亚硝基二甲胺(NDMA)导致氧化DNA损伤显著增加,最低有效浓度分别为5 mM和27 mM。NPYR比NDMA具有更强的遗传毒性作用。在有或没有Fpg酶存在的情况下,所测试的任何浓度的有机硫化合物(OSCs)本身均未引起DNA损伤。当HepG2细胞同时用OSCs和N-亚硝胺处理时,OSCs(二烯丙基硫醚,DAS和二丙基硫醚,DPS,1-50 microM;二烯丙基二硫醚,DADS和二丙基二硫醚,DPDS,1-5 microM)以剂量依赖的方式降低了N-亚硝胺的遗传毒性作用。分别用最高浓度的DAS(50 microM)和DADS(5 microM)时,NPYR的作用分别减弱了约61-67%。DADS(5 microM,66%)对NDMA诱导的氧化DNA损伤的保护作用高于DAS(50 microM,53%)。50 microM的DPS和5 microM的DPDS浓度分别使NPYR/NDMA诱导的氧化DNA损伤降低了65-63%和59-65%。我们的结果表明,OSCs可保护人源细胞免受环境中存在的两种致癌化合物NPYR和NDMA的氧化DNA损伤作用。