Tumor Promoting Effect of Phenolphthalein on Development of Lung Tumors Induced by N-ethyl-N-nitrosourea in Transgenic Mice Carrying Human Prototype c-Ha-ras Gene

Abstract

In order to examine tumor modifying effects of phenolphthalein (PhP), female transgenic mice carrying human prototype c-Ha-ras gene (rasH2 mice) were given a single intraperitoneal injection of 60 mg/kg body weight of N-ethyl-N-nitrosourea (ENU), followed by the diet containing 12,000 ppm PhP for 26-week. Histopathologically, alveolar hyperplasias, adenomas and adenocarcinomas were observed in the ENU + PhP group, but only hyperplasias and adenomas were observed in the ENU alone group. The incidence and multiplicity of adenocarcinomas in the ENU + PhP group was significantly increased as compared to that in the ENU alone group. The combined multiplicity of adenomas and adenocarcinomas in this group was also significantly higher than that of the ENU alone group. In addition, the ratio of area of adenomas in the ENU + PhP group was significantly higher than that in the ENU alone group. The result of our study suggests that PhP has a clear tumor promoting effect in the lung of rasH2 mice.