Effects of sodium butyrate and 3-aminobenzamide on survival of Chinese hamster HA-1 cells after X irradiation.
HA-1 cells were grown in medium containing 2 mM sodium butyrate and then exposed to graded doses of 250 kVp X rays. After irradiation, some of the butyrate-treated cultures were treated with either 10 or 20 mM 3-aminobenzamide for 2 h at 37 degrees C. The butyrate treatment produced a small degree of radiation sensitization as indicated by an increase in the alpha parameter using a linear-quadratic description of survival responses. The dose-modifying factor at the 10% survival level (DMF10) was 1.15. Similarly, both 10 and 20 mM 3-aminobenzamide treatments produced concentration-dependent increases in radiosensitization, again as indicated by an increase in the value of the alpha constant, with DMF10 values of 1.22 and 1.40, respectively. However, the combination of the 2 mM sodium butyrate + 10 mM 3-aminobenzamide treatments produced a supraadditive response in terms of increased cell killing (DMF10 = 1.76). We interpret this to mean that 3-aminobenzamide inhibits a sodium butyrate associated increase in poly(ADP-ribose) which then predisposes hyperacetylated chromatin to attack by endogenous nucleases leading to increased cytotoxicity.
Leith
J T
JT
Department of Radiation Medicine and Biology Research, Brown University, Providence, Rhode Island.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D066298:In Vitro Techniques; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
D001549:Benzamides; D002087:Butyrates; D011838:Radiation-Sensitizing Agents; D020148:Butyric Acid; C025160:3-aminobenzamide