Journal Article

Rapid induction of uterine tumors with p53 point mutations in heterozygous p53-deficient CBA mice given a single intraperitoneal administration of <i>N</i>-ethyl-<i>N</i>-nitrosourea

Kunitoshi Mitsumori, Hiroshi Onodera, Takeo Shimo, Kazuo Yasuhara, Hisayoshi Takagi, Takatoshi Koujitani, Masao Hirose, Chika Maruyama and Shigeharu Wakana

in Carcinogenesis

Volume 21, issue 5, pages 1039-1042
Published in print May 2000 | ISSN: 0143-3334
Published online May 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.5.1039
Rapid induction of uterine tumors with p53 point mutations in heterozygous p53-deficient CBA mice given a single intraperitoneal administration of N-ethyl-N-nitrosourea

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To investigate the sensitivity of heterozygous p53-deficient CBA mice to carcinogens, 20 female mice [p53(+/–)] and 20 wild-type littermates [p53(+/+)] were given an intraperitoneal injection of 120 mg/kg body wt of N-ethyl-N-nitrosourea (ENU) and were maintained without any other treatment for a further 26 weeks. Histopathology showed that uterine tumors (endometrial polyps and stromal sarcomas) and lung adenomas were induced in both p53(+/–) and p53(+/+) mice. The incidence of uterine tumors and lung adenomas (94% and 81%, respectively) in p53(+/–) mice was significantly greater than that in p53 (+/+) mice (37% and 42%, respectively). Malignant lymphomas were only induced in p53(+/–) mice, at an incidence of 31%. Concerning uterine tumors and preneoplastic lesions, there were endometrial stromal sarcomas and atypical hyperplasias of the endometrial gland in 90% and 63%, respectively, of p53(+/–) mice, with significantly greater incidences than in p53(+/+) mice. Gene analysis revealed GCG→GTG point mutations in codon 135 of exon 5 of the p53 allele in all of the uterine endometrial stromal sarcomas examined. Our results suggest that female p53(+/–) CBA mice are very susceptible to uterine carcinogenesis, providing a useful model for ENU-induced uterine tumors.

Keywords: ENU, N-ethyl-N-nitrosourea; MNU, N-methyl-N-nitrosourea.

Journal Article.  3368 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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