Murphy S E, Heiblum R, King P G, Bowman D, Davis W J, Stoner G D
Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, NY 10595.
Carcinogenesis. 1991 Jun;12(6):957-61. doi: 10.1093/carcin/12.6.957.
The effect of phenethyl isothiocyanate (PEITC) on the metabolism of N'-nitrosonornicotine (NNN) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by cultured rat oral tissue was investigated. Two protocols were used. In one, oral tissue from untreated rats was cultured in the presence of 10 or 50 microM PEITC and either NNN or NNK. The levels of NNN and NNK metabolites released into the culture media were determined by HPLC analysis. The presence of 10 microM PEITC inhibited the formation of all NNN metabolites from 45 to 70% when the concentration of NNN was 1 microM or 10 microM. When the concentration of PEITC was 50 microM the extent of inhibition was from 70 to 90%. alpha-Hydroxylation of NNK was inhibited 70 to 90% and N-oxidation of NNK was inhibited 80 to 90% by 10 microM PEITC. Carbonyl reduction of NNK to NNAL was unaffected by 10 microM PEITC and only slightly inhibited by 50 microM PEITC. In the second protocol, rats were fed NIH-07 diet containing 3 mumol PEITC/g for 1-14 days. The metabolism of NNN by cultured oral tissue from these rats was decreased from 40 to 90% relative to that by tissue from control rats. NNK metabolism was inhibited 40 to 60%. The extent of inhibition was the same when rats were fed PEITC containing diet for 1 or 14 days. NNN and NNK are the only tobacco constituents which induce oral cavity cancer in an animal model. The results of this study suggest the possibility that PEITC may be useful as a chemopreventive agent for oral cavity cancer.
研究了苯乙基异硫氰酸酯（PEITC）对培养的大鼠口腔组织代谢N'-亚硝基降烟碱（NNN）和4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮（NNK）的影响。采用了两种方案。在一种方案中，将未处理大鼠的口腔组织在含有10或50微摩尔PEITC以及NNN或NNK的条件下培养。通过高效液相色谱分析测定释放到培养基中的NNN和NNK代谢物水平。当NNN浓度为1微摩尔或10微摩尔时，10微摩尔PEITC的存在将所有NNN代谢物的形成抑制了45%至70%。当PEITC浓度为50微摩尔时，抑制程度为70%至90%。10微摩尔PEITC将NNK的α-羟基化抑制了70%至90%，并将NNK的N-氧化抑制了80%至90%。NNK羰基还原为NNAL不受10微摩尔PEITC影响，仅受50微摩尔PEITC轻微抑制。在第二种方案中，给大鼠喂食含3微摩尔PEITC/克的NIH-07饮食1至14天。与对照大鼠的组织相比，这些大鼠培养的口腔组织对NNN的代谢降低了40%至90%。NNK代谢受到40%至60%的抑制。当给大鼠喂食含PEITC的饮食1天或14天时，抑制程度相同。NNN和NNK是仅有的在动物模型中诱发口腔癌的烟草成分。本研究结果表明PEITC有可能作为口腔癌的化学预防剂。
