Mechanism of differential efficacy of garlic organosulfides in preventing benzo(a)pyrene-induced cancer in mice.
Mechanism of differential efficacy of garlic organosulfides in preventing benzo(a)pyrene-induced cancer in mice.
复制标题
大蒜有机硫化物预防苯并（a）芘诱导的小鼠癌症的差异功效机制。
DOI：
10.1016/s0304-3835(97)00237-1
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发表时间：
1997
期刊：
影响因子：
9.7
通讯作者：
Singh,SV
中科院分区：
文献类型：
--
作者：
Srivastava,SK;Hu,X;Xia,H;Zaren,HA;Chatterjee,ML;Agarwal,R;Singh,SV
通过测定二烯丙基硫醚（DAS）、二烯丙基二硫醚（DADS）、二烯丙基三硫醚（DATS）、二丙基硫醚（DPS）和二丙基二硫醚（DPDS）对苯并（a）芘（BP）诱发的小鼠肿瘤的影响，探讨了它们对BP激活/失活途径中酶的影响。除DATS外，用其他有机硫化物（OSC）处理小鼠导致肝脏乙氧基试卤灵O-脱乙基酶（EROD）活性小幅但显著增加（37-44%）。然而，前胃EROD活性在对照组和处理组之间没有显著差异。只有DAS治疗导致肺EROD活性适度但具有统计学意义的降低（约25%）。这些结果表明，虽然EROD活性的降低可能，至少部分，有助于DAS介导的抑制BP诱导的肺癌，抗致癌作用的OSC对BP诱导的前胃癌似乎是独立的这种机制。与对照组相比，DAS、DADS和DATS处理小鼠导致两个肝脏中的（分别为3.0、3.2和4.4倍）和前胃抗7β，8 α-二羟基-9 α，10 α-氧代-7，8，9，10-四氢苯并（a）芘谷胱甘肽转移酶（GST）活性分别为1.5、2.7和2.7倍（抗BPDE），这是BP的最终致癌物。肺GST活性没有增加任何的OSC。即使环氧化物水解酶（EH）活性的差异改变这些OSC，OSC的化学预防功效和他们对EH活性的影响之间的相关性并不明显。本研究的结果表明，在能力的差异的OSC调节GST活性对抗BPDE可能，至少部分地，占其差异化学预防功效对BP诱导的癌症小鼠。
The mechanism of differential efficacies of diallyl sulfide (DAS), diallyl disulfide (DADS), diallyl trisulfide (DATS), dipropyl sulfide (DPS) and dipropyl disulfide (DPDS) in preventing benzo(a)pyrene (BP)-induced cancer in mice has been investigated by determining their effects on the enzymes of BP activation/inactivation pathways. With the exception of DATS, treatment of mice with other organosulfides (OSCs) caused a small but significant increase (37–44%) in hepatic ethoxyresorufin O-deethylase (EROD) activity. However, the forestomach EROD activity did not differ significantly between control and treated groups. Only DAS treatment caused a modest but statistically significant reduction (about 25%) in pulmonary EROD activity. These results suggest that while reduction of EROD activity may, at least in part, contribute to the DAS-mediated inhibition of BP-induced lung cancer, anticarcinogenic effects of OSCs against BP-induced forestomach carcinogenesis seems to be independent of this mechanism. Treatment of mice with DAS, DADS and DATS resulted in a significant increase, as compared with control, in both hepatic (3.0-, 3.2- and 4.4-fold, respectively) and forestomach (1.5-, 2.7- and 2.7-fold, respectively) glutathione transferase (GST) activity toward anti-7β,8α-dihydroxy-9α,10α-oxy-7,8,9,10-tetrahydrobenzo (a)pyrene (anti-BPDE), which is the ultimate carcinogen of BP. The pulmonary GST activity was not increased by any of the OSCs. Even though epoxide hydrolase (EH) activity was differentially altered by these OSCs, a correlation between chemopreventive efficacy of OSCs and their effects on EH activity was not apparent. The results of the present study suggest that differences in the ability of OSCs to modulate GST activity toward anti-BPDE may, at least in part, account for their differential chemopreventive efficacy against BP-induced cancer in mice.