Lack of susceptibility of transgenic mice carrying the human c-Ha-ras proto-oncogene (rasH2 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 heterozygous p53-deficient female mice at the same dose in a 6-month study. To examine whether phenolphthalein carcinogenic potential can be detected in male and female transgenic (Tg) mice carrying the human c-Ha-ras gene (rasH2 mice) and their wild-type littermates (non-Tg mice), a diet containing 3000, 6000 or 12000 ppm was given for 6 months. Unequivocal induction of neoplastic lesions was not apparent, suggesting that rasH2 mice are resistant to the induction of malignant lymphomas by the treatment of phenolphthalein.
Koujitani
T
T
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, Japan.
Yasuhara
K
K
Usui
T
T
Nomura
T
T
Onodera
H
H
Takagi
H
H
Hirose
M
M
Mitsumori
K
K
D018248:Adenoma, Liver Cell / Q000139:chemically induced; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests / Q000379:methods*; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006394:Hemangiosarcoma / Q000139:chemically induced; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced; D008223:Lymphoma / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020113:Phenolphthalein / Q000633:toxicity*; D000090063:Proto-Oncogene Mas; D013160:Splenic Neoplasms / Q000139:chemically induced; D013953:Thymus Neoplasms / Q000139:chemically induced; D013997:Time Factors
D002273:Carcinogens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020113:Phenolphthalein