Contrasting effects of the differentiating agent sodium butyrate on recovery processes after x-irradiation in heterogeneous human colon tumor cells

Abstract

The X ray survival responses of two clonal subpopulations of cells (clones A and D) from a heterogeneous human colon adenocarcinoma (DLD-1) were studied in unfed plateau phase cultures either as control cultures or in cultures grown for three passages in medium containing the differentiating agent sodium butyrate (NaB, 2 mM). Specifically, the cultures were studied with regard to their ability to express both potentially lethal and sublethal damage recovery (PLDR and SLDR). Growth in NaB-containing medium enhanced the radiation sensitivity of both cell lines in the low dose (“shoulder”) region of the survival curve. For clone A, the Dq value was reduced by 59%, and for clone D, the Dq value was reduced by 96%. NaB treatment increased both the rate and the extent of PLDR in both cell lines as assessed by single dose kinetic studies. However, when split dose experiments are performed to assess the expression of SLDR, NaB pretreatment was shown to totally inhibit the expression of SLDR, and also to alter the expression of PLDR under these conditions. These data suggest that PLDR and SLDR are separate, yet related, cellular recovery processes. In addition, NaB may be useful as an adjunct to radiotherapy by virtue of its ability to sensitize tumor cells in the dose range conventionally used for therapy, as well as by inhibition of sublethal damage recovery.