Induction of micronuclei in CHO cells by bleomycin but not by X-irradiation is decreased by treatment with HMG-CoA reductase inhibitors.
We investigated the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and fluvastatin, on the induction of micronuclei by ionizing radiation or bleomycin in Chinese hamster ovary cells in order to assess the radical-scavenging ability of these inhibitors. The results indicated that both pravastatin and fluvastatin had no effect on the induction of micronuclei by X-irradiation when they were applied for either pre-treatment or post-treatment. In contrast, both drugs effectively reduced the frequency of bleomycin-induced micronuclei when they were applied for simultaneous treatment or post-treatment, but not for pre-treatment. This indicates that the radical-scavenging ability of these two HMG-CoA reductase inhibitors differs according to the origins of the radicals--e.g., X-rays or bleomycin--even when the two drugs are compared at an equivalent cytotoxic dose. Our results suggest that both pravastatin and fluvastatin have the ability to scavenge certain types of radicals and to protect cells against oxidative stress.
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Japan.
Junji
J
Iwashita
Seiji
S
Kodama
Mikiro
M
Nakashima
Hitoshi
H
Sasaki
Kotaro
K
Taniyama
Masami
M
Watanabe
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage*; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced / Q000187:drug effects* / Q000528:radiation effects*; D017035:Pravastatin / Q000008:administration & dosage*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000528:radiation effects; D014965:X-Rays / Q000009:adverse effects*
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D001761:Bleomycin; D000077340:Fluvastatin; D017035:Pravastatin