Differential repair of 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea-induced DNA damage in two human colon tumor cell lines.

Two human colon tumor cell lines were examined for their responses to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea treatment when maintained as cultured cell lines and xenograft tumors in nude mice. One tumor line, HT, was resistant to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea treatment both in tissue culture and in vivo. The other tumor line, BE, was sensitive to 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea treatment in vitro and in vivo. The DNA of tissue-cultured cells treated with 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea was examined by alkaline elution for DNA damage. 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea was found to produce DNA strand breaks and DNA cross-links in both cell types. The DNA cross-links appear to be completely repaired in the resistant HT line over the 48-hr period following drug removal, but in the sensitive BE line little or no cross-link repair was observed during this interval.