Carcinogenesis, Vol 19, 1141-1147, Copyright © 1998 by Oxford University Press
A DuBowski, DA Johnston, T Rupp, L Beltran, CJ Conti and J DiGiovanni
The current study was designed to further establish that most papillomas
produced in SENCAR mice during two-stage skin carcinogenesis are, in fact,
premalignant lesions and to specifically determine the malignant conversion
potential of papillomas that arise at different times during the
carcinogenesis process. A method was established to physically map and
monitor the lifespan of all papillomas produced in SENCAR mice during the
course of an initiation-promotion experiment using DMBA as the initiator
and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The results
from these experiments showed that in groups of mice initiated with either
0.5 or 2.0 microg DMBA, long- term (60 weeks) treatment with TPA yielded a
significantly higher number of SCCs compared to short-term treatment (7
weeks). Papillomas that emerged after 11 weeks and thereafter in all
treatment groups had the ability to progress to SCCs. The median conversion
time for all papillomas in all groups was 26 weeks. When corrected for
median conversion time, papillomas that emerged in week 11 and thereafter
in all treatment groups had similar or greater conversion ratios compared
to those that emerged within the first 10 weeks. Interestingly, the median
conversion time was significantly shorter (18 versus 27 weeks,
respectively; P<0.0002) for papillomas that emerged in week 11 and
thereafter compared to those that emerged at or prior to 10 weeks for all
groups. The data in this study demonstrate that papillomas arising
throughout a two-stage carcinogenesis protocol in SENCAR mice progress to
SCCs. Many papillomas that arise later in two-stage carcinogenesis
protocols do not have sufficient time to allow for conversion and should be
excluded from the analyses. Furthermore, another novel finding of the
current study was the observation that papillomas arising later in the
two-stage protocol (>11 weeks) progressed to SCCs at a faster rate than
those that arose earliest in the protocol.
ARTICLES
Papillomas at high risk for malignant progression arising both early and late during two-stage carcinogenesis in SENCAR mice
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville 78957, USA.
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