Dose-response relationship for induction of solid tumors in female B6C3F1 mice irradiated neonatally with a single dose of gamma rays.

Abstract

Our previous studies showed that mice during infancy are highly susceptible to the induction of several types of solid tumors. The present study was designed to elucidate the dose-response relationships for induction of solid tumors after exposure to 0.48-5.70 Gy of 137Cs gamma rays in the neonatal period in female mice. A total of 2988 mice were allowed to live out their life span under a specific pathogen free condition and lifetime incidences of liver, pituitary, ovarian, lung and bone tumors were recorded. The dose-response curves for liver, pituitary, ovarian and lung tumors were convex upward in the dose range examined, and were composed of three parts: an initial rapid increase of incidence at doses below 1 Gy, a gradual increase to the highest incidence, and a decrease in incidence with increasing dose in the higher dose range. The dose which induces neoplasm at the highest incidence seemed to be different for each type of solid tumor. The shape of the dose-response curve for induction of bone tumors was quite different from that for other solid tumors; the initial slope of the curve was concave upward. Dose-response relationships were analyzed using a model that allows for tumorigenic effect, inactivation of potentially tumorigenic cells and competing risks. The results showed that the tumorigenic effect was proportional to the dose of gamma rays for induction of liver, pituitary, ovarian and lung tumors; whereas the tumorigenic effect for bone tumors was proportional to the square of the dose. A significant increase in incidence was also found for gastrointestinal tumors, kidney tumors, adrenal tumors and hemangiomas of spleen, although dose-response relationships could not be analyzed.