Radioprotective properties of DNA methylation-disrupting agents.
5-Azacytidine and sodium butyrate, two DNA methylation-disrupting agents, were tested for radioprotective properties on V79A03 cells. Both compounds can activate genes not previously expressed (e.g. metallothionein). 5-Azacytidine treatment (3 microM, 24 h) caused a 50% decrease in the 5-methylcytosine content of V79A03 DNA whereas sodium butyrate treatment (1 mM, 24h) resulted in a 700% increase in 5-methylcytosine content. Additionally, 5-azacytidine treatment resulted in the increased survival of V79A03 cells, with treatment 24 h prior to exposure to gamma radiation providing a dose reduction factor of 1.8. Sodium butyrate treatment did not result in a significant increase in survival. These results indicate that the hypomethylation of genomic DNA prior to exposure to gamma radiation correlates with an increase in survival of V79A03 cells, possibly due to the activation of the enzymes involved in repair.
Kalinich
J F
JF
Radiation Biochemistry Department, Armed Forces Radiobiology Research Institute, NNMC-NCR, Bethesda, MD 20889-5145.
Catravas
G N
GN
Snyder
S L
SL
D044503:5-Methylcytosine; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002470:Cell Survival / Q000528:radiation effects; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D003864:Depression, Chemical; D066298:In Vitro Techniques; D008745:Methylation; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013268:Stimulation, Chemical
D002087:Butyrates; D011837:Radiation-Protective Agents; D020148:Butyric Acid; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA; D001374:Azacitidine