Changes in X-ray sensitivity and glutathione content of human colon tumor cells after exposure to the differentiation-inducing agent sodium butyrate.
Clone A human colon cancer cells were exposed to concentrations of sodium butyrate (NAB, 0-2 mM) for three passages in vitro, and responses to either graded single doses or split doses of 250 kVp X rays were determined. The survival data were fit to the single-hit, multitarget model of inactivation. For the graded single dose experiments, we found that NAB produced a decrease in the magnitude of the quasi-threshold (Dq) parameter after a concentration of about 0.9 mM was exceeded. Similarly, in split dose experiments, the amount of sublethal damage recovery (SLDR) was reduced in a concentration-dependent manner as shown by a decrease in the Dq parameter. However, the inhibition of SLDR occurred with no apparent threshold NAB concentration. NAB did not affect potentially lethal damage recovery. Paradoxically, increasing concentrations of NAB produced an exponential increase in the intracellular glutathione content, which could be blocked by exposure of the cells to buthionine sulfoximine (BSO). BSO treatment of NAB-adapted cells led to additional cell killing, again most noted by changes in the Dq parameter. We postulate that these responses are associated with NAB-induced changes in chromatin structure, particularly the association between DNA and nucleosomal histones H3 and H4.
Leith
J T
JT
Radiation Biology Laboratories, Brown University, Providence, Rhode Island 02902.
Hallows
K T
KT
Arundel
C M
CM
Bliven
S F
SF
D019328:Buthionine Sulfoximine; D002087:Butyrates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000473:pathology; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects
D002087:Butyrates; D004273:DNA, Neoplasm; D020148:Butyric Acid; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione