Precancerous mammary hyperplastic alveolar nodules in four strains of virgin mice with different mammary tumor potentials: influence of chronic caffeine ingestion.

Based on the stimulating effects of caffeine on the formation of precancerous mammary hyperplastic alveolar nodules (HAN) in mice, the onset time of HAN was estimated by chronic caffeine ingestion in four strains of virgin mice with varying mammary tumor potentials (SHN, SLN, GR/A and C3H/He). Beginning at 21 days of age at weaning, mice were given tap water with (0.05%) or without caffeine and were killed at 40, 60, 90, 120 and/or 150 days of age. In the caffeine-treated groups, HAN appeared at 60, 120, 60 and 90 days of age in SHN, SLN, GR/A and C3H/He, respectively, while no such changes developed in the controls at the respective ages. These are the consequence of stimulation by caffeine of the growth of very early foci of HAN and indicate that HAN appear after 40, 90, 40 and 60 days of age in SHN, SLN, GR/A and C3H/He, respectively. The onset time of HAN is associated with mammary tumor potential of virgin mice. Caffeine did not affect estrous cycle, plasma levels of prolactin and growth hormone and endocrine organ weights, suggesting that promotion by caffeine of HAN growth is minimally mediated by the endocrine system.