Carcinogenesis, Vol 18, 497-502, Copyright © 1997 by Oxford University Press
SK Katiyar, RR Mohan, R Agarwal and H Mukhtar
We earlier showed that a polyphenolic fraction isolated from green tea
(GTP) affords protection against tumor promotion and tumor progression in
SENCAR mouse skin. The present study was designed to further evaluate the
protective effect of GTP against the induction and subsequent progression
of papillomas to squamous cell carcinomas (SCCs) in experimental protocols
where papillomas were developed with a low or high probability of their
malignant conversion. Topical application of GTP (6 mg/animal) 30 min prior
to that of 12-O-tetradecanoylphorbol-13- acetate (TPA) either once a week
for 5 weeks (high risk TPA protocol) or once a week for 20 weeks (low risk
TPA protocol) or mezerein (MEZ) twice a week for 20 weeks (high risk MEZ
protocol) in 7,12- dimethylbenz[a]anthracene (DMBA)-initiated mouse skin
resulted in significant protection against skin tumor promotion in terms of
tumor incidence (32-60%), multiplicity (49-63%) and tumor volume/mouse (73-
90%) at the termination of the experiment at 20 weeks. In three separate
malignant progression experiments when papilloma yield in DMBA- initiated
and TPA or MEZ promoted low and high risk protocols was stabilized at 20
weeks, animals were divided into two subgroups. These animals were either
topically treated twice weekly with acetone (0.2 ml/animal, spontaneous
malignant conversion group) or with GTP (6 mg/animal in 0.2 ml acetone) for
an additional period of 31 weeks. During these treatment regimens, all
suspected carcinomas were recorded and each one was verified
histopathologically either at the time when tumor-bearing mouse
died/moribund or at the termination of the experiment at 51 weeks. GTP
resulted in significant protection against the malignant conversion of
papillomas to SCC in all the protocols employed. At the termination of the
experiment at 51 weeks, these protective effects were evident in terms of
mice with carcinomas (35- 41%), carcinomas per mouse (47-55%) and percent
malignant conversion of papillomas to carcinomas (47-58%). The kinetics of
malignant conversion suggest that a subset of papillomas formed in the
early phase of tumor promotion in all the protocols had a higher
probability of malignant conversion into SCCs because all the positive
control groups (acetone treated) produced nearly the same number of
carcinomas (33-38 in a group of 20 animals) at the end of the progression
period. In the GTP- treated group of animals the number of carcinomas
formed was less (14- 20 in a group of 20 animals), which shows the ability
of GTP to protect against the malignant conversion of papillomas of higher
probability of malignant conversion to SCCs. The results of this study
suggest that irrespective of the risk involved, GTP may be highly useful in
affording protection against skin cancer risk.
ARTICLES
Protection against induction of mouse skin papillomas with low and high risk of conversion to malignancy by green tea polyphenols
Department of Dermatology, Case Western Reserve University, Cleveland, OH 44106-5028, USA.
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