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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate (DMBA-TPA)
Published on: December 19, 2019
Preventive effects of lupeol on DMBA induced DNA alkylation damage in mouse skin
Nidhi Nigam1, Sahdeo Prasad, Yogeshwer Shukla
1Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow 226001, India.
Abstract:
Mutations that occur through DNA strand breaks are the precursors of the variety of genetic disorders including cancer. Life style and dietary habits are considered as major determinants in causation and prevention of genetic diseases. Epidemiological and laboratory studies suggest that plant derived compounds have the potential to prevent a number of genetic diseases. Therefore, use of nutraceuticals can be an important and convenient tool for chemoprevention. Polyphenolic phytochemicals such as epigallocatechin gallate flavonoids quercetin, genistein, curcumin and resveratrol constitute a class of nutraceuticals with notable efficacy in preclinical models of carcinogenesis. Lupeol, a pentacyclic triterpene present in mango, is a biologically active compound that has been reported to possess a number of pharmacological properties in the in vivo and in vitro studies. In the present study, we investigated the effects of lupeol on 7,12-dimethylbenz[a]anthracene (DMBA), induced DNA strand breaks in mouse skin, using an alkaline unwinding assay. Increasing doses of lupeol (50-200 microg/mouse) were given topically, prior or after the single topical application of DMBA (100 microg/mouse) with the sampling time of 24, 48, 72 and 96 h, respectively. Both pre and post treatment of lupeol showed significant (p<0.001) preventive effects in DMBA induced DNA strand breaks in dose and time dependent manner. The pre-treatment of lupeol at the dose of 200 microg/mouse showed 56.05% prevention, and post-treatment at the same dose showed 43.26% prevention, at 96 h time interval, against DMBA induced DNA strand breakage. The results suggest preventive effects of lupeol on DMBA induced DNA alkylation damage in Swiss albino mice.
Insights
Lupeol, a compound from mango, significantly prevents DNA strand breaks caused by DMBA in mice. This nutraceutical shows dose- and time-dependent protective effects, suggesting potential for chemoprevention against genetic damage.
Area of Science:
- Biochemistry
- Molecular Biology
- Toxicology
Background:
- DNA strand breaks are precursors to genetic disorders like cancer.
- Lifestyle and diet influence genetic disease risk and prevention.
- Plant-derived compounds and nutraceuticals show promise for chemoprevention.
Purpose of the Study:
- To investigate the chemopreventive effects of lupeol against DMBA-induced DNA strand breaks in mouse skin.
- To evaluate lupeol's efficacy as a topical agent for DNA damage prevention.
Main Methods:
- Swiss albino mice were subjected to topical application of 7,12-dimethylbenz[a]anthracene (DMBA).
- Lupeol was administered topically at varying doses (50-200 microg/mouse) before or after DMBA exposure.
- DNA strand breaks were quantified using an alkaline unwinding assay at different time points (24-96 h).
Main Results:
- Both pre- and post-treatment with lupeol demonstrated significant (p<0.001) preventive effects against DMBA-induced DNA strand breaks.
- Prevention was observed in a dose- and time-dependent manner.
- At 96 h, 200 microg/mouse of lupeol provided 56.05% prevention with pre-treatment and 43.26% with post-treatment.
Conclusions:
- Lupeol exhibits significant chemopreventive properties against DMBA-induced DNA damage in mouse skin.
- The findings support lupeol's potential as a topical agent for mitigating DNA alkylation damage.
- Lupeol represents a promising nutraceutical for the prevention of chemically induced genetic damage.

