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The effect of age, fractionation, and dose on radiation carcinogenesis in various tissues of mice.

C57BL/6 × C3H F1 mice were exposed postnatally to ionizing radiation for investigation of the role of postnatal age periods, fractionation schedule, and to a lesser degree the dose on carcinogenesis in various tissues. Starting on the 1st, 15th, or 42nd day of age, 4 experimental series were exposed to a total dose of 320 R, delivered in either single or fractionated exposures (4 or 7 days apart), and 1 series received 480 R in 4 weekly exposures. Mice were killed at 86 weeks of age, and their tumor response was compared with tumor incidence of control animals sacrificed at the identical age and with that of mice sacrificed at 56 weeks of age or observed to 166th week of life.

Malignant lymphomas, hepatomas, lung adenomas, Harderian gland cystadenomas, and ovarian tumors were the most frequently observed cancers. They developed “spontaneously” late in life. Their development was accelerated and/or enhanced by irradiation. Lung adenomas and malignant lymphomas occurred with similar incidence regardless of age at irradiation. Incidence of Harderian gland and ovarian tumors increased, while development of hepatomas decreased with increase in age of animals at the time of irradiation. Newborn and infant male mice developed significantly more hepatomas than females. All other tumor types emerged with similar incidence in both sexes.

The variation in the fractionation schedule had modifying effect upon development of leukemia, hepatomas, and ovarian tumors. Fifty % increase in the irradiation dose strikingly further enhanced leukemogenesis but not the development of other tumors.

The spectrum of tumors which developed in irradiated C57BL/6 × C3H F1 mice by the 86th week of life resembled the tumor profile observed in 166-week-old nonirradiated controls. The expression of oncogenic capabilities in several tissues was accelerated by the ionizing radiation, the degree of which was dependent upon the age at irradiation, fractionation schedule, and/or total radiation dose delivered.