Carcinogenic comparative study on rasH2 mice produced by two breeding facilities.

CByB6F1-Tg(HRAS)2Jic mice (brand name: rasH2 mouse) are produced by two breeding facilities, CLEA Japan, Inc. (Fuji, Shizuoka, Japan) and Taconic (Germantown, NY, USA), and supplied world wide. To confirm carcinogenic conformity of both mice, a 26-week carcinogenicity test was performed on a total of 120 mice obtained from both facilities under the same protocol and same timing in our facility.

Examination of percutaneous application in a 26-week carcinogenicity test in CB6F1-TG rasH2 mice.

We examined the possibility of expanding applications of rasH2 mice, which are genetically manipulated mice for short-term carcinogenicity tests, to percutaneous application. A 26-week short-term carcinogenicity study was performed on a total of 300 mice including 75 male and female rasH2 mice each, and 75 male and female non-Tg mice each from the same litter as the rasH2 mice divided into untreated group, an ethanol group, a white Vaseline group, an acetone group, and a phorbol 12-myristate 13-acetate (TPA) group. Only shaving of dorsal skin was performed on the untreated mice.

Use of IC tags in short-term carcinogenicity study on CB6F1 TGrasH2 mice.

We studied the effect of IC tags, subcutaneously implanted animal identification tools, on rasH2 mice. A 26-week short-term carcinogenicity study was performed on a total of 299 mice including 75 male and female rasH2 mice each, and 74 male and 75 female non-Tg mice from the same litter as the rasH2 mice divided into a non-IC tag group, the IC-tag group, acetone group, TPA group and MNU group (all of the animals except for those in the non-IC tag group) had IC tags implanted subcutaneously in their backs. The administration methods of the positive control drugs TPA (2.

Phenotypic abnormalities observed in aged cloned mice from embryonic stem cells after long-term maintenance.

Somatic/embryonic stem cell cloning has made it possible to produce an individual genomically identical to another individual. However, the cloned animals have a variety of abnormalities caused by the aberrant gene modification, with insufficient reprogramming in cloning. We previously reported abnormalities in cloned mice at birth.

Mutation analysis of vinyl carbamate or urethane induced lung tumors in rasH2 transgenic mice.

Previous studies showed that significant differences in mutation frequency of the human c-Ha-ras transgene between vinyl carbamate (VC)- and ethyl carbamate (urethane)-induced lung tumors were observed in rasH2 mice. It remains unclear why the point mutation frequency is extremely low in VC-induced lung tumors, although this compound is much more carcinogenic than urethane. In this study, we examined the somatic point mutations of the transgene at the RNA level in VC- and urethane-induced lung tumors of rasH2 mice.

Interlaboratory comparison of short-term carcinogenicity studies using CB6F1-rasH2 transgenic mice.

In order to evaluate a short-term carcinogenicity testing system using CB6F1 -Tg rasH2 (rasH2-Tg) mice carrying a human prototype c-Ha-ras gene, 26-week studies were conducted in 12 different facilities as a part of an International Life Science Institute Health and Environmental Science Institute (ILSI HESI) international collaborative project. In each study N-methyl-N-nitrosourea (MNU) was administered to a separate group of rasH2-Tg mice by single intraperitoneal injection (75 mg/kg) as a positive control. We herein have summarized the mortality, body weight change, and neoplastic and nonneoplastic lesions detected in these positive control groups as representative historical positive control data.

Lack of susceptibility of heterozygous p53-knockout CBA and CIEA mice to phenolphthalein in a 6-month carcinogenicity study.

Phenolphthalein has carcinogenic activity, causing malignant lymphomas in B6C3F1 mice at a dietary dose of 3000 ppm in a 2-year carcinogenicity study and in female heterozygous p53-knockout TSG mice (C57BL/6 background) at the same dose in a 6-month study. To examine whether carcinogenic potential of phenolphthalein can be detected in other p53-knockout mouse [p53 (+/-)] strains such as p53 (+/-) CBA mice or p53 (+/-) CIEA mice (C57BL/6 background) and their littermates, they were given a diet containing 0, 6000 or 12000 ppm for 6 months. Unequivocal induction of neoplastic lesions was not apparent, suggesting that p53 (+/-) CBA mice and p53 (+/-) CIEA mice are resistant to the induction of malignant lymphomas by the treatment of phenolphthalein.

Skeletal myopathy in transgenic mice carrying human prototype c-Ha-ras gene.

Skeletal myopathy was found in almost all-transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mouse). Microscopically, variation of the muscle fiber size, centrally placed nuclei, regenerating fibers, and interstitial fibrosis were evident; hyalinization and necrosis were sometimes observed in the skeletal muscle (femoralis and pectoralis) of the rasH2 mice. Inflammatory changes in the skeletal muscle or abnormality of adjacent peripheral nerve were not observed.

The Tg rasH2 mouse in cancer hazard identification.

The Tg rasH2 transgenic mouse has been developed as an altemative to the lifetime mouse bioassay to predict the carcinogenic potential of chemicals. Unlike the p53+/- mouse, the Tg rasH2 mouse is sensitive to both genotoxic and nongenotoxic carcinogens. The Tg rasH2 mouse, officially designated CB6F1-TgN (RasH2), contains multiple copies of the human c-Ha-ras oncogene and promoter within its genome.