Age at Exposure and the Late Effects of X-Rays. Survival and Tumor Incidence in CAF 1 Mice Irradiated at 1 to 2 Years of Age

Abstract

Survival and tumor incidence at autopsy were studied in the adult CAF1 mouse irradiated at various ages. The ages at exposure, in so far as such a comparison can be made, bracket a period equivalent to that of about 18 to 65 years in man. Neither the Gompertz equation nor the probit transform of cumulative percent mortality describes the life table accurately regardless of strain and age at exposure. The probit for CAF1 mice was practically a linear function of time after exposure at either 5 or 12 months of age, but not afterward. In the case of log central death rate as a function of post-exposure time x, the best fit for unirradiated CAF1 mice was of the form - A + Bx - Cx2 (between 400 and 1250 days of age, the period of sufficient CAF1 data). For comparisons, median or mean survival time, or the relative odds of mortality and its associated x2 were used. In general, irradiation of old adults tended to have less life-shortening effect than irradiation of young adults. During much of adult life the female reacted as if sensitized to low doses (e.g., below 250 rads). The slope of the female dose-effect curve between 250 and 500 rads, however, was less than that of the male. Late in life the CAF1 female may become less sensitive than the male. These effects were correlated with changes in endocrine balance secondary to ovarian damage that would not be expected to occur in women. Life shortening was not associated with increased neoplasia in "older" CAF1 and BALB/c mice, but with a decrease. In the CAF1, irradiation tended to reduce the number of decedents with tumors rather than to reduce the number of tumors per tumor-bearing decedent, and the tumorous animal lived as long or longer than the non-tumorous one. The irradiated mouse is in certain specific respects an abnormal mouse and also one that is aging in an abnormal way. Usually, but not necessarily, it dies sooner than usual, depending in part on age at exposure and sex, as well as on radiation dose. It appears reasonable that the hazard of inducing late effects in man is reduced when irradiation occurs in the latter part of life and when the dose is relatively small.