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

• Published in: Carcinogenesis (New York) 2000-05, Vol.21 (5), p.1039-1042
• Main Authors: Mitsumori, Kunitoshi, Onodera, Hiroshi, Shimo, Takeo, Yasuhara, Kazuo, Takagi, Hisayoshi, Koujitani, Takatoshi, Hirose, Masao, Maruyama, Chika, Wakana, Shigeharu
• Format: Article
• Language: English
• Subjects: Animal tumors. Experimental tumors; Animals; Base Sequence; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens - toxicity; Chemical agents; DNA Primers; ENU; Ethylnitrosourea - toxicity; Experimental genital and mammary tumors; Female; Genes, p53; Heterozygote; Injections, Intraperitoneal; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; MNU; N-ethyl-N-nitrosourea; N-methyl-N-nitrosourea; Point Mutation; Polymerase Chain Reaction; Tumors; Uterine Neoplasms - chemically induced; Uterine Neoplasms - genetics
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/21.5.1039

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.