Importance of mammary gland DNA synthesis on carcinogen-induced mammary tumorigenesis in rats.
DNA synthesis in mammary gland estimated by [3H]thymidine incorporation was significantly higher on the day of proestrus than on the second day of diestrus in 50-day-old female Sprague-Dawley rats. The percentage of progressive mammary tumors, tumor growth rate, and the number and the weight of tumors per tumor-bearing rat were significantly higher in the animals given a single i.v. injection of 5 mg 7,12-dimethylbenz(a)anthracene at proestrus than in the animals given it at diestrus. Inhibition of DNA synthesis at proestrus by 2-bromo-alpha-ergocryptine also suppressed mammary tumorigenesis by the carcinogen. In 90-day-old rats in which little difference was found in mammary gland DNA synthesis between proestrus and diestrus, there was no difference in mammary tumorigenesis between animals given the carcinogen at proestrus and animals given it at diestrus. On the other hand, the prestimulation of mammary gland DNA synthesis by prolactin increased the growth, the number, and the weight of carcinogen-induced mammary tumors. These results demonstrate the importance of mammary DNA synthesis at the time when a carcinogen acts on the glands in mammary tumorigenesis.