Temporal sequence of mammary intraductal proliferations, ductal carcinomas in situ and adenocarcinomas induced by 1-methyl-1- nitrosourea in rats

An experimental model for mammary carcinogenesis has been described inwhich intraductal proliferations, ductal carcinomas in situ andadenocarcinomas can be readily detected and the frequency of theiroccurrence quantified. The objective of the experiment reported in thisstudy was to determine the latency period between carcinogen administrationand the occurrence of each of these types of lesion. A total of 150 femaleSprague-Dawley rats were injected i.p. with 50 mg 1- methyl-1-nitrosourea(MNU)/kg body wt at 21 days of age. Groups of 30 rats each were killed at7, 14, 21, 28 and 35 days post-carcinogen. Mammary intraductalproliferations were the first detected lesions and were observed in 20% ofthe animals at 14 days following carcinogen administration. At 21 dayspost-carcinogen ductal carcinomas in situ and adenocarcinomas wereobserved. The number of each type of lesion increased with timepost-carcinogen, but the temporal pattern of occurrence was different amonglesion types. The pattern of lesion occurrence was consistent withintraductal proliferations being a precursor lesion for ductal carcinomasin situ and adenocarcinomas. Furthermore, the data imply that ductalcarcinomas in situ represent one pathway of morphological progression bywhich intraductal proliferations evolve into invasive carcinomas, but thatthis lesion type, as currently defined histologically, may not be anobligatory intermediate in morphologic progression. These findings areconsistent with emerging evidence of multiple but distinct pathogeneticpathways leading to mammary carcinomas that display different morphologicalpatterns and biological activities.