Mereto E, Frencia L, Ghia M
Institute of Pharmacology, University of Genoa, Italy.
Cancer Lett. 1994 Jan 15;76(1):5-9. doi: 10.1016/0304-3835(94)90127-9.
The aim of this work was to investigate if the possible chemopreventive effect of aspirin (ASA) on rat colon carcinogenesis could be detected with a medium-term assay. The end-point chosen was the inhibition of incidence and growth of putative preneoplastic lesions, the aberrant crypt foci (ACF) induced in the rat colon by two administrations of 1,2-dimethylhydrazine (DMH, 25 mg/kg p.o.). At both 4 and 8 weeks after the starting of the carcinogenic treatment the incidence of total ACF was reduced of 60% in rats receiving ASA (10 mg/kg/day p.o.) for 12 consecutive days during the initiation treatment with DMH. Also the number of the larger foci (with 3 or more crypts) was significantly lower in ASA-treated rats at both time-points (about 70% reduction). Moreover, concomitant ASA treatment determined a significant decrease of the mean number of crypts per focus at week 8. These results indicate that the chemopreventive effect of ASA on chemically-induced rat colon carcinogenesis observed in long-term studies may be detected in this relatively short assay.
本研究旨在探讨能否通过中期试验检测阿司匹林(ASA)对大鼠结肠癌发生的潜在化学预防作用。所选择的终点是抑制假定的癌前病变即1,2 - 二甲基肼(DMH,25mg/kg口服)两次给药诱导的大鼠结肠异常隐窝灶(ACF)的发生率和生长。在致癌处理开始后的第4周和第8周,在DMH启动处理期间连续12天接受ASA(10mg/kg/天口服)的大鼠中,总ACF的发生率降低了60%。在这两个时间点,接受ASA处理的大鼠中较大隐窝灶(有3个或更多隐窝)的数量也显著更低(减少约70%)。此外,在第8周时,同时进行的ASA处理使每个隐窝灶的平均隐窝数量显著减少。这些结果表明,在长期研究中观察到的ASA对化学诱导的大鼠结肠癌发生的化学预防作用,在这个相对较短的试验中可能被检测到。