Phenethyl isotiocyanate modulates clastogenicity of mitomycin C and cyclophosphamide in vivo

Soumitra Sen , Anita Mukherjee, Kalpana Agarwal, Archana Sharma
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引用次数: 13

Abstract

Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables, is an effective chemopreventive agent against N-nitrosamine-induced carcinogenesis. We have investigated the extent to which PEITC modulates the clastogenicity of standard genotoxicants, mitomycin C and cyclophosphamide, using bone marrow cells of Swiss albino mice. PEITC, 1 μmol/kg body weight in corn oil was administered by gavage for 7 consecutive days to prime the animals. 24 h later, mice received a single dose of cyclophosphamide (10 or 20 mg/kg body weight)or mitomycin C (1 or 2 mg/kg body weight) intraperitoneally. Clastogenicity of the chemicals was compared using PEITC-primed and non-primed animals 24 h after clastogen treatment. As a single agent, PEITC is not clastogenic even after 7 days of priming. Oral priming with PEITC decreased the aberrations per cell values by 22–67% in all cases. PEITC could only alleviate the clastogenicity of I mg/kg body weight mitomycin C to near-control values (p ≤ 0.05). Although PEITC is reported to be effective against N-nitrosamine-induced tumorigenesis by preventing metabolic activation and by blocking the reactive species formed, it is virtually ineffective against the clastogenicity of cyclophosphamide. The results of inhibition by PIETC of the clastogenicity of mitomycin C suggest that the modulation of mitomycin C bio-activation contributes to, but may not be sufficient for, PIETC chemoprevention of clastogenicity by mitomycin C.

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异氰酸苯乙酯在体内调节丝裂霉素C和环磷酰胺的致裂性
异硫氰酸苯乙酯(Phenethyl isothiocyanate, PEITC)是十字花科蔬菜中含有的一种有效的化学防癌剂,可预防n -亚硝胺引起的癌变。我们已经研究了PEITC调节标准基因毒素丝裂霉素C和环磷酰胺的致裂性的程度,使用瑞士白化小鼠的骨髓细胞。以1 μmol/kg体重的玉米油灌胃PEITC,连续灌胃7 d。24 h后,小鼠腹腔注射单剂量环磷酰胺(10或20 mg/kg体重)或丝裂霉素C(1或2 mg/kg体重)。在致裂剂处理24 h后,用peitc引物和未引物的动物对化学物质的致裂性进行比较。作为单一制剂,PEITC即使在启动7天后也不具有致裂性。在所有病例中,口服PEITC使每个细胞的畸变值降低了22-67%。PEITC仅能将1 mg/kg体重丝裂霉素C的致裂性降低至接近控制值(p≤0.05)。尽管据报道,PEITC通过阻止代谢激活和阻断形成的活性物质对n -亚硝胺诱导的肿瘤发生有效,但它实际上对环磷酰胺的致裂性无效。PIETC对丝裂霉素C致裂性的抑制结果表明,调节丝裂霉素C的生物活性有助于PIETC对丝裂霉素C致裂性的化学预防,但可能并不充分。
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