Study on the effect of atorvastatin on 7, 12-Dimethylbez(a)anthracene and croton oil induced skin tumorigenesis in the mice

Abstract

Intrduction: Cancer incidence is one of the human problems and in order to understand its mechanistic aspects several studies have been performed. Objective: In this study we showed that atorvastatin has essential role in mice skin carcinogenesis. Methods & Materials: Eighty female Albino Swiss mice were divided into 4 groups and the back of the mice were shaved with Moser set and hair remover cream. After 24 hours, the animals of groups 2, 3, 4 received 3 doses of 100, 200 and 300 µg of atorvastatin topically for 15 days. As a pretreatment study, atorvastatin was applied before using Dimethylbenz (a) anthracene (DMBA). Twenty four hours after application of final dose, the mice of all groups were initiated by a single dose of DMBA (60g/100l acetone/mouse). After 7 days, animals were promoted topically by croton oil (0.5mg/200l acetone/mouse) twice weekly for period of 32 weeks. Results: At the end of 8th week the first tumors were observed in the group of animals receiving atorvastatin plus DMBA and promoted with croton oil. However in the control group (DMBA+Croton oil), the tumor occurred at week 10. Also both in number and percentage of tumor incidence significantly were higher in group receiving atorvastatin (300 µg) at various intervals of times. Discussion: The resµlts obtained from this study showed that atorvastatin coµld exacerbate skin tumors in comparison to the control group. Overall, our study demonstrates that atorvastatin in its high dose is responsible for mouse skin carcinogenesis. The role of excessive doses of atorvastatin in mice skin induction may be due to its potential capabilities of producing oxidative stress injuries and DNA damage. However, the exact mechanism of tumor induction by atorvastatin remains elusive and needs further experimentations.