Preferential Induction of Mammary Tumors in p53 Hemizygous BALB/c Mice by Fractionated Irradiation of a Sub-lethal Dose of X-rays

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  • MORI NOBUKO
    Research Institute for Advanced Science & Technology, Osaka Prefecture University
  • YAMATE JYOJI
    Department of Veterinary Pathology, Graduate School of Agricultural Lifesciences, Osaka Prefecture University
  • UMESAKO SEI-ICHI
    Research Institute for Advanced Science & Technology, Osaka Prefecture University
  • HONG DOO-PYO
    Research Institute for Advanced Science & Technology, Osaka Prefecture University
  • OKUMOTO MASAAKI
    Research Institute for Advanced Science & Technology, Osaka Prefecture University
  • NAKAO REN
    Research Institute for Advanced Science & Technology, Osaka Prefecture University

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Abstract

BALB/c mice are susceptible to radiation-induced mammary tumors as well as lymphomas. We investigated the effects of the p53 deficient allele and of X-irradiation on the tumor spectrum in the BALB/c background. Substantially all p53 -/-animals died of thymic lymphomas before 36 weeks of age, while none of the p53 +/+ animals died during that period. At this age, mortalities of p53 +/- females and males were 5% (1/22) and 11% (1/9), respectively, due to non-thymic lymphoma and sarcoma. When exposed to 4 Gy of X-irradiation, 100% (44/44) and 95% (18/19) of p53 +/- mice died with tumors within 36 weeks. Among these, the predominant cause of death was lymphoma in either sex [26/44 (59%) in females; 13/19 (68%) in males]; mammary adenocarcinoma (15/44, 34%) and sarcoma (3/19, 16%) were semi-dominant in females and males, respectively. The mortalities of similarly treated p53 +/+ mice were 16% (5/31) in females and 17% (3/18) in males: virtually all deaths were due to thymic lymphomas in either sex. When exposed to 4 ¤ 0.7 Gy of X-irradiation at weekly intervals, 23/23 (100%) of the p53 +/-females died of tumors within 36 weeks. In these animals, mammary adenocarcinoma (15/23, 65%), instead of lymphoma (7/23, 30%), was dominant. None of the similarly treated p53 +/+ females developed malignant tumors during the period. Mammary adenocarcinomas generated in p53 +/- females exposed or non-exposed to radiation showed a frequent loss of the p53 wild-type allele. Hence, we provided a useful experimental system to study radiation-induced mammary tumors in mice.<br>

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