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Carcinogenesis, Vol. 20, No. 6, 997-1003, June 1999
© 1999 Oxford University Press

Molecular Epidemiology and Cancer Prevention

Chemopreventive effect of 4'-demethyl epipodophyllotoxin on DMBA/TPA-induced mouse skin carcinogenesis

Deepika Dhawan, Sivaprakasam Balasubramanian, Ashok J. Amonkar1 and Neeta Singh2

Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029 and
1 Cancer Research Institute, Parel Mumbai, India

The chemopreventive effect of topical application of 4'-demethyl epipodophyllotoxin (DMEP), an antimitotic agent, on a two-stage skin carcinogenesis model in Swiss Albino mice induced by 9,10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) was investigated. Two topical applications with 0.24% DMBA over 1 week, followed later by 5 nmol of TPA twice weekly produced 100% incidence of tumors in these animals by 18 weeks. Treatment of animals with DMEP (until the end of the experiment), 30 min before TPA treatment, significantly reduced the tumor incidence, tumor volume and the conversion efficiency of papillomas to squamous cell carcinomas. The tumor formation and growth was also delayed by DMEP pre-treatment. Application of DMEP protected against the losses provoked in levels of glutathione and activity of catalase and superoxide dismutase in skin and liver of animals by the application of DMBA/TPA. Thus, DMEP might possibly be exerting its chemopreventive activity by acting as an antioxidant.

Abbreviations: CAT, catalase; DMBA, 9,10-dimethylbenz[a]anthracene; DMEP, 4'-demethyl epipodophyllotoxin; GSH, glutathione; MDA, malondialdehyde; ROS, reactive oxygen species; SOD, superoxide dismutase; TPA, 12-O-tetradecanoylphorbol-13-acetate.

2 To whom correspondence should be addressed Email: neeta{at}medinst.ernet.in


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