PHENETHYL ISOTIOCYANATE MODULATES CLASTOGENICITY OF MITOMYCIN-C AND CYCLOPHOSPHAMIDE IN-VIVO

Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous ve getables, 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 a nd cyclophosphamide, using bone marrow cells of Swiss albino mice. PEI TC, 1 mu mol/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 mitomyc in C (1 or 2 mg/kg body weight) intraperitoneally. Clastogenicity of t he chemicals was compared using PEITC-primed and non-primed animals 24 h after clastogen treatment. As a single agent, PEITC is not clastoge nic even after 7 days of priming. Oral priming with PEITC decreased th e aberrations per cell values by 22-67% in all cases. PEITC could only alleviate the clastogenicity of 1 mg/kg body weight mitomycin C to ne ar-control values (p less than or equal to 0.05). Although PEITC is re ported to be effective against N-nitrosamine-induced tumorigenesis by preventing metabolic activation and by blocking the reactive species f ormed, it is virtually ineffective against the clastogenicity of cyclo phosphamide. The results of inhibition by PIETC of the clastogenicity of mitomycin C suggest that the modulation of mitomycin C bio-activati on contributes to, but may not be sufficient for, PIETC chemopreventio n of clastogenicity by mitomycin C.