Preventive effects of lupeol on DMBA induced DNA alkylation damage in mouse skin.
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.
Nigam
Nidhi
N
Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, P.O. Box 80, M.G. Marg, Lucknow 226001, India.
Prasad
Sahdeo
S
Shukla
Yogeshwer
Y
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000287:Administration, Topical; D000478:Alkylation / Q000187:drug effects; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D051379:Mice; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D014315:Triterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000094042:Lupanes
D015127:9,10-Dimethyl-1,2-benzanthracene; D002273:Carcinogens; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C010480:lupeol; D000094042:Lupanes