Peto R, Roe F J, Lee P N, Levy L, Clack J
Br J Cancer. 1975 Oct;32(4):411-26. doi: 10.1038/bjc.1975.242.
In an experiment involving 950 mice with a normal lifespan of 2-3 years, in laboratory conditions, regular benzpyrene application to the skin was started at 10, 25, 40 or 55 weeks of age. The incidence rate of malignant epithelial tumours among the survivors in each group increased steeply with time. This increase was associated directly with duration of exposure but, given duration, was independent of age at the start of exposure, as were the growth rates of already established tumours. In our experiment, although age per se was irrelevant, the cancer incidence rate increased approximately as a power of the duration of exposure to benzpyrene. This shows that the observed approximate power-law increase of most human adult cancer incidence rates with age could exist merely because age equals duration of exposure to background and spontaneous carcinogenic stimuli. Thus, no intrinsic effects of ageing (such as failing immunological surveillance or age related hormonal changes) whatever need to postulated to explain the vast increases in old age of the incidence rates of such human cancers. This result can greatly simplify speculation about mechanisms of carcinogenesis.
在一项涉及950只正常寿命为2至3年的小鼠的实验中,在实验室条件下,分别在10周、25周、40周或55周龄开始定期将苯并芘涂抹于小鼠皮肤。每组存活小鼠中恶性上皮肿瘤的发病率随时间急剧上升。这种上升与暴露持续时间直接相关,但在暴露持续时间一定的情况下,与开始暴露时的年龄无关,已形成肿瘤的生长速率也是如此。在我们的实验中,虽然年龄本身无关紧要,但癌症发病率大约随苯并芘暴露持续时间的幂次增加。这表明,观察到的大多数人类成年癌症发病率随年龄增长近似幂律增加,可能仅仅是因为年龄等于暴露于背景和自发致癌刺激的持续时间。因此,无需假定衰老的任何内在影响(如免疫监视功能衰退或与年龄相关的激素变化)来解释此类人类癌症在老年时发病率的大幅上升。这一结果可大大简化对致癌机制的推测。