Carcinogenesis, Vol 19, 2181-2185, Copyright © 1998 by Oxford University Press
HJ Thompson, JN McGinley, P Wolfe, M Singh, VE Steele and GJ Kelloff
An experimental model for mammary carcinogenesis has been described in
which intraductal proliferations, ductal carcinomas in situ and
adenocarcinomas can be readily detected and the frequency of their
occurrence quantified. The objective of the experiment reported in this
study was to determine the latency period between carcinogen administration
and the occurrence of each of these types of lesion. A total of 150 female
Sprague-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 at
7, 14, 21, 28 and 35 days post-carcinogen. Mammary intraductal
proliferations were the first detected lesions and were observed in 20% of
the animals at 14 days following carcinogen administration. At 21 days
post-carcinogen ductal carcinomas in situ and adenocarcinomas were
observed. The number of each type of lesion increased with time
post-carcinogen, but the temporal pattern of occurrence was different among
lesion types. The pattern of lesion occurrence was consistent with
intraductal proliferations being a precursor lesion for ductal carcinomas
in situ and adenocarcinomas. Furthermore, the data imply that ductal
carcinomas in situ represent one pathway of morphological progression by
which intraductal proliferations evolve into invasive carcinomas, but that
this lesion type, as currently defined histologically, may not be an
obligatory intermediate in morphologic progression. These findings are
consistent with emerging evidence of multiple but distinct pathogenetic
pathways leading to mammary carcinomas that display different morphological
patterns and biological activities.
ARTICLES
Temporal sequence of mammary intraductal proliferations, ductal carcinomas in situ and adenocarcinomas induced by 1-methyl-1- nitrosourea in rats
Centers for Cancer Causation and Prevention, AMC Cancer Research Center, Lakewood, CO 80214, USA.
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