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 B 6C3F1 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 de tected 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 con taining 3000, 6000 or 12 000 ppm was given for 6 months. Unequivocal induct ion of neoplastic lesions was not apparent, suggesting that rasH2 mice are resistant to the induction of malignant lymphomas by the treatment of pheno lphthalein. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.