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.