A comparative study on the antimutagenicity of atorvastatin and lovastatin against directly acting mutagens.
Elevated levels of oxidative DNA lesions have been noted in many tumors and such damage is strongly implicated in the etiology of cancer. The cumulative risk of cancer increases with the fourth power of age and is associated with an accumulation of oxidative DNA damage. Many agents, synthetic or natural, that can inhibit mutation have been depicted as cancer chemopreventive agents. Antimutagenicity of the 3-hydroxy-3-methylgutaryl-CoA (HMG-CoA) reductase inhibitors atorvastatin and lovastatin was studied using the Ames Salmonella typhimurium assay. Directly acting mutagens, sodium azide (NaN(3)) and 4-nitro-o-phenylenediamine (NPDA), were used to induce mutation in Salmonella strains TA98 and TA100. The antimutagenicity of lovastatin and atorvastatin was found to be significant (p < 0.01) and dose-dependent. The percentage inhibition of a 3 mg lovastatin-treated plate was found to be 79.9% and 61.8% against NPDA- and NaN(3)-induced mutation to TA98 and TA100, respectively. Atorvastatin (0.5 mg/plate) inhibited NPDA-and NaN(3)-induced mutation to TA98 and TA100 by 78.6% and 45.5%, respectively. Atorvastatin showed antimutagenic activity at lower concentrations than lovatstatin. The results of the present study regarding the antimutagenic activity of atorvastatin and lovastatin suggested their therapeutic application as cancer chemopreventive agents.
Ajith
T A
TA
Department of Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Thrissur, Kerala, India. taajith@rediffmail.com
Soja
M
M
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D008148:Lovastatin / Q000494:pharmacology*; D016296:Mutagenesis; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens; D009154:Mutation; D011758:Pyrroles / Q000494:pharmacology*; D012475:Salmonella / Q000378:metabolism; D012486:Salmonella typhimurium / Q000378:metabolism
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D006538:Heptanoic Acids; D009153:Mutagens; D011758:Pyrroles; D008148:Lovastatin; D000069059:Atorvastatin