Son H Y, Nishikawa A, Furukawa F, Lee I S, Ikeda T, Miyauchi M, Nakamura H, Hirose M
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-8501, Tokyo, Japan.
Cancer Lett. 2000 Nov 28;160(2):141-7. doi: 10.1016/s0304-3835(00)00570-x.
The modifying effects of dietary 4-phenylbutyl isothiocyanate (PBITC), given during the initiation stage of carcinogenesis, were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). A total of 120 female 5-week-old hamsters were divided into six groups. Animals in groups 1-3, each consisting of 30 hamsters, were given BOP by two subcutaneous injections, 1 week apart, at a dose of 20 mg/kg body weight, plus 0, 10 or 100 micromol/animal of PBITC in corn oil by gavage 2 h prior to each carcinogen treatment. Ten animals in group 4 served as a vehicle control, and animals in groups 5 and 6, each consisting of ten hamsters, were given 10 and 100 micromol of PBITC alone in corn oil. Sacrifice was 52 weeks after the first BOP injection. The PBITC treatments significantly (P<0.05) inhibited the development of pancreatic ductal dysplasias and adenocarcinomas. Also, lung tumors (adenomas and adenocarcinomas) were significantly (P<0.05) reduced in a dose-dependent manner. In contrast, both hepatocellular and cholangiocellular tumors (adenomas and carcinomas) tended to be or were significantly increased by PBITC. These results, taken together with our previous findings, indicate that the natural isothiocyanate, phenethyl isothiocyanate (PEITC), has a more potent chemopreventive action against BOP-induced tumorigenesis than synthetic isothiocyanates with longer alkyl chains, such as 3-phenylpropyl isothiocyanate (PPITC) and PBITC. Thus, their lipophilicity does not necessarily reflect the chemopreventive potential because the strength of lipophilicity is PEITC<PPITC<PBITC.
研究了在致癌作用起始阶段给予膳食4-苯基丁基异硫氰酸酯（PBITC）对经N-亚硝基双（2-氧代丙基）胺（BOP）处理的仓鼠的影响。总共120只5周龄雌性仓鼠被分为六组。第1 - 3组每组30只仓鼠，在间隔1周的时间里通过两次皮下注射给予BOP，剂量为20 mg/kg体重，并且在每次致癌物处理前2小时通过灌胃给予玉米油中0、10或100 μmol/只的PBITC。第4组的10只动物作为溶媒对照，第5组和第6组每组10只动物，仅给予玉米油中10和100 μmol的PBITC。在首次注射BOP后52周处死动物。PBITC处理显著（P<0.05）抑制了胰腺导管发育异常和腺癌的发生。此外，肺肿瘤（腺瘤和腺癌）也显著（P<0.05）以剂量依赖方式减少。相比之下，PBITC使肝细胞瘤和胆管细胞肿瘤（腺瘤和癌）有增加趋势或显著增加。这些结果与我们之前的发现一起表明，天然异硫氰酸酯苯乙基异硫氰酸酯（PEITC）对BOP诱导的肿瘤发生的化学预防作用比具有更长烷基链的合成异硫氰酸酯如3-苯基丙基异硫氰酸酯（PPITC）和PBITC更强。因此，它们的亲脂性不一定反映化学预防潜力，因为亲脂性强度为PEITC<PPITC<PBITC。
