Preferential induction of mammary tumors in p53 hemizygous BALB/c mice by fractionated irradiation of a sub-lethal dose of X-rays.
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 currency 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.
Mori
Nobuko
N
Research Institute for Advanced Science & Technology, Osaka Prefecture University, Osaka, Japan. morin@riast.osakfu-u.ac.jp
Yamate
Jyoji
J
Umesako
Sei-ichi
S
Hong
Doo-Pyo
DP
Okumoto
Masaaki
M
Nakao
Ren
R
D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism*; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007928:Lethal Dose 50; D008223:Lymphoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D012509:Sarcoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012737:Sex Factors; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*; D014965:X-Rays / Q000009:adverse effects*
D016159:Tumor Suppressor Protein p53