Dihydropyridines decrease X-ray-induced DNA base damage in mammalian cells.
Compounds with the structural motif of 1,4-dihydropyridine display a broad spectrum of biological activities, often defined as bioprotective. Among them are L-type calcium channel blockers, however, also derivatives which do not block calcium channels exert various effects at the cellular and organismal levels. We examined the effect of sodium 3,5-bis-ethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine-4-carboxylate (denoted here as DHP and previously also as AV-153) on X-ray-induced DNA damage and mutation frequency at the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) locus in Chinese hamster ovary CHO-K1 cells. Using formamido-pyrimidine glycosylase (FPG) comet assay, we found that 1-h DHP (10nM) treatment before X-irradiation considerably reduced the initial level of FPG-recognized DNA base damage, which was consistent with decreased 8-oxo-7,8-dihydro-2'-deoxyguanosine content and mutation frequency lowered by about 40%. No effect on single strand break rejoining or on cell survival was observed. Similar base damage-protective effect was observed for two calcium channel blockers: nifedipine (structurally similar to DHP) or verapamil (structurally unrelated). So far, the specificity of the DHP-caused reduction in DNA damage - practically limited to base damage - has no satisfactory explanation.
Wojewódzka
M
M
Center of Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa, Poland. marylaw@ichtj.waw.pl
Gradzka
I
I
Buraczewska
I
I
Brzóska
K
K
Sochanowicz
B
B
Goncharova
R
R
Kuzhir
T
T
Szumiel
I
I
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D016466:CHO Cells / Q000528:radiation effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D009154:Mutation; D014965:X-Rays / Q000009:adverse effects*
D016587:Antimutagenic Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines