Hecht S S, Chung F L, Richie J P, Akerkar S A, Borukhova A, Skowronski L, Carmella S G
American Health Foundation, Valhalla, New York 10595, USA.
Cancer Epidemiol Biomarkers Prev. 1995 Dec;4(8):877-84.
Epidemiological studies indicate that vegetable consumption protects against lung cancer in humans, but the protective constituents have not been identified. Phenethyl isothiocyanate (PEITC), which is release upon chewing of watercress (nasturtium officinale), is a chemopreventive agent against lung cancer induced by the tobacco-specific lung carcinogen 4- (methylnitrosamino)-1-(3-pyridyl-1-butanone (NNK) in rats and mice. PEITC inhibits the carcinogenicity of NNK by inhibiting its metabolic activation and thereby increasing the levels of detoxified metabolites excreted in urine. In this study, our goal was to determine whether watercress consumption would modify NNK metabolism in smokers. Eleven smokers maintained constant smoking habits and avoided cruciferous vegetables and other sources of isothiocyanates throughout the study. They donated 24-h urine samples on 3 consecutive days (baseline period). One to 3 days later, they consumed 2 ounces (56.8 g) of watercress at each meal for 3 days and donated 24-h urine samples on each of these days (watercress consumption period). One and 2 weeks later, they again donated 24-h urine samples on 2-3 consecutive days (follow-up periods). The samples were analyzed for two metabolites of NNK; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and [4-methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-omega-D-glucosiduro nic acid (NNAL- Gluc). NNAL-Gluc is believed to be a detoxification product of NNK. The urine samples were also analyzed for PEITC-NAC, a metabolite of PEITC. Minimum exposure to PEITC during the watercress consumption period averaged 19-38 mg/day. Seven of the 11 subjects had increased levels of urinary NNAL plus NNAL-Gluc on days 2 and 3 of the watercress consumption period, compared to the baseline period. Overall, the increase in urinary NNAL plus NNAL-Gluc in this period was significant [mean +/- SD 0.924 +/- 1.12 nmol/24 h (33.5%); P < 0.01]. Urinary levels of NNAl plus NNAL-Gluc returned to near baseline levels in the follow-up periods. The percentage of increase in urinary NNAL plus NNAL-Gluc during days 2 and 3 of the watercress consumption period correlated with intake of PEITC during this period, as measured by total urinary PEITC-NAC (r = 0.62; P = 0.04). The results of this study support our hypothesis that PEITC inhibits this oxidative metabolism of NNK in humans, as seen in rodents, and support further development of PEITC as a chemopreventive agent against lung cancer. This is the first study to report an effect of vegetable consumption on metabolism of a lung carcinogen in humans.
流行病学研究表明，食用蔬菜可预防人类患肺癌，但其中的保护成分尚未明确。苯乙基异硫氰酸酯（PEITC）是在咀嚼水田芥（豆瓣菜）时释放出来的，它是一种化学预防剂，可预防大鼠和小鼠中由烟草特异性肺癌致癌物4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮（NNK）诱发的肺癌。PEITC通过抑制NNK的代谢活化来抑制其致癌性，从而增加尿液中排出的解毒代谢物水平。在本研究中，我们的目标是确定食用水田芥是否会改变吸烟者体内NNK的代谢。11名吸烟者在整个研究过程中保持恒定的吸烟习惯，并避免食用十字花科蔬菜和其他异硫氰酸酯来源。他们在连续3天（基线期）捐赠了24小时尿液样本。1至3天后，他们每餐食用2盎司（56.8克）水田芥，持续3天，并在这些日子的每一天都捐赠24小时尿液样本（食用水田芥期）。1周和2周后，他们又在连续2至3天捐赠了24小时尿液样本（随访期）。对样本进行了NNK的两种代谢物分析；4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁醇（NNAL）和[4-甲基亚硝基氨基）-1-（3-吡啶基）丁-1-基]-β-ω-D-葡萄糖醛酸（NNAL-葡糖苷酸）。NNAL-葡糖苷酸被认为是NNK的解毒产物。还对尿液样本进行了PEITC-NAC（PEITC的一种代谢物）分析。食用水田芥期间PEITC的最低暴露量平均为19 - 38毫克/天。与基线期相比，11名受试者中有7名在食用水田芥期的第2天和第3天尿中NNAL加NNAL-葡糖苷酸水平升高。总体而言，这一时期尿中NNAL加NNAL-葡糖苷酸的增加具有显著性[平均值±标准差0.924±1.12纳摩尔/24小时（33.5%）；P<0.01]。在随访期，尿中NNAl加NNAL-葡糖苷酸水平恢复到接近基线水平。食用水田芥期第2天和第3天尿中NNAL加NNAL-葡糖苷酸增加的百分比与该时期PEITC的摄入量相关，以尿中总PEITC-NAC衡量（r = 0.62；P = 0.04）。本研究结果支持我们的假设，即PEITC在人类中抑制NNK的这种氧化代谢（如在啮齿动物中所见），并支持将PEITC进一步开发为预防肺癌的化学预防剂。这是第一项报告食用蔬菜对人类肺癌致癌物代谢有影响的研究。
