Comparison of the Teratogenic Actions of Adenine and Methyixanthine Compounds in Mice

Abstract

The present investigation was undertaken to compare embryopathic, or teratogenic activities in mice of methylxanthines such as caffeine, theophylline and theobromine and of adenine. Sublethal dosages of these compounds were intraperitoneally administered to JCL: ICR mice on day 9 or day 12 of gestation. Fetuses were grossly and skeletally examined on day 18 of gestation. Main results were as follows.
1. Caffeine, theophylline, theobromine and adenin e induced significantly high frequencies of malformed fetuses mainly with axial skeletal defects when they were administered on day 9 of gestation. In addition, adenine caused various types of gross malformations.
2. When these chemicals were injected on day 12 of gestation, they also produced significantly high frequencies of abnormal fetuses mostly with cleft palate and/or subcutaneous hematoma. However, each incidence of abnormality varied with the cornpound injected.
3. A s each type of embryopathic effects caused by these compounds is compared, the effects of caffeine, theophylline and theobromine on the developing embryos resembled each other. However, the effects of adenine differed from them in terms of low maternal toxicity and high embryopathic activities. The mechanism of embryopathic activities of adenine may be different from that of methylxanthines.