Morse M A, Eklind K I, Amin S G, Hecht S S, Chung F L
Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, NY 10595.
Carcinogenesis. 1989 Sep;10(9):1757-9. doi: 10.1093/carcin/10.9.1757.
Six homologous arylakyl isothiocyanates were evaluated for their abilities to inhibit pulmonary adenomas induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice. Four consecutive daily doses (5 mumol/mouse) of phenyl isothiocyanate (PITC), benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), 3-phenylpropyl isothiocyanate (PPITC), 4-phenylbutyl isothiocyanate (PBITC), 4-oxo-4-(3-pyridyl)-butyl isothiocyanate (OPBITC) and corn oil were administered to mice by gavage. Two hours following the final dosing, mice were administered saline or 10 mumol of NNK in saline i.p. Pulmonary adenomas were counted at 16 weeks after NNK administration. The mice administered only corn oil prior to NNK developed an average multiplicity of 9.2 tumors/mouse. Pretreatment with PITC, BITC and OPBITC had no significant effects on NNK-induced lung neoplasia. However, PEITC pretreatment resulted in a 64% reduction of lung tumor multiplicity, but did not affect the percentage of mice that developed tumors. Both PPITC and PBITC decreased tumor multiplicity by 96% and the percentage of tumor-bearing animals by greater than 60%. These results, in conjunction with our previous work, demonstrate a general trend of increasing inhibition of NNK-induced lung neoplasia by arylalkyl isothiocyanates with increasing alkyl chain length. This study also demonstrates the remarkable inhibitory activities of PPITC and PBITC, two isothiocyanates that had not previously been tested as chemopreventive agents.
评估了六种同源芳基烷基异硫氰酸酯抑制烟草特异性亚硝胺4-(甲基亚硝胺)-1-(3-吡啶基)-1-丁酮(NNK)诱导A/J小鼠肺腺瘤的能力。通过灌胃给小鼠连续四天每日剂量(5 μmol/小鼠)的苯基异硫氰酸酯(PITC)、苄基异硫氰酸酯(BITC)、苯乙基异硫氰酸酯(PEITC)、3-苯丙基异硫氰酸酯(PPITC)、4-苯丁基异硫氰酸酯(PBITC)、4-氧代-4-(3-吡啶基)-丁基异硫氰酸酯(OPBITC)和玉米油。末次给药后两小时，给小鼠腹腔注射生理盐水或10 μmol NNK的生理盐水溶液。在给予NNK后16周时计数肺腺瘤。在给予NNK之前仅给予玉米油的小鼠平均每只发生9.2个肿瘤。用PITC、BITC和OPBITC预处理对NNK诱导的肺肿瘤形成没有显著影响。然而，PEITC预处理使肺肿瘤的多灶性降低了64%，但不影响发生肿瘤的小鼠百分比。PPITC和PBITC均使肿瘤多灶性降低了96%，使荷瘤动物百分比降低了60%以上。这些结果与我们之前的工作一起表明了一个总体趋势，即芳基烷基异硫氰酸酯对NNK诱导的肺肿瘤形成的抑制作用随着烷基链长度的增加而增强。本研究还证明了PPITC和PBITC这两种异硫氰酸酯具有显著的抑制活性，它们以前未作为化学预防剂进行过测试。
