The rate of progression of radiation-transformed mammary epithelial cells is enhanced after low-dose-rate neutron irradiation

Studies in this laboratory have shown enhancement of the mammary tumorigenic effects of neutron irradiation after low-dose-rate neutron exposures. To investigate possible reasons, a mammary cell system was used which allows quantitation of initiated mammary epithelial cells and examination of the progression of these radiation-altered cells toward the neoplastic phenotype. Female BALB/c mice were irradiated with fission-spectrum neutrons at dose rates of 1 rad/minor 1 rad/day. Twenty-four hours or 16 weeks after irradiation, mammary cells were obtained by enzymatic dissociation. Mammary outgrowths were derived by injection of 10⁴ cells into gland-free fat pads of 3-week-old female BALB/c mice. The frequency of ductal dysplasias in outgrowths from cell irradiated at high or low dose rates was similar. Persistence of dysplasias differed markedly. Few of the dysplasias in outhts growths derived from cells irradiated at the high dose rate persisted, while a large fraction of the dysplasias in outgrowths derived from cell irradiated at low dose rate persisted. When cells remained in situ for 16 weeks prior to dissociation a higher frequency of persistent altered cells was also observed in outgrowths derived from cells irradiated at low neutron dose rates. These data suggest that low-dose-rate neutron exposures enhance the probability of progression of carcinogen-altered cells rather than increase the numbers of initiated cells.