DNA DAMAGE AND REPAIR IN L1210 CELLS EXPOSED TO 1-(2-CHLOROETHYL)-3-CYCLOHEXYL-1-NITROSOUREA

Abstract

The DNA of L1210 cells [mouse leukemia] exposed to low concentrations of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was analyzed for the presence of single strand breaks. DNA from 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea treated cells sediments more slowly than control DNA on alkaline sucrose gradients and shows a greater extent of strand separation of the DNA helix in alkali. These effects are a typical result of exposure of cellular DNA to alkylating agents or ionizing radiation. The extent of DNA damage caused by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea was related to the same amount of damage resulting from exposure of cells to low doses of .gamma.-irradiation. The rate and extent of repair of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea induced damage is slow and incomplete, compared with the repair of .gamma.-irradiation damage to DNA. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea behaves as a weak alkylating agent, a property that may explain its antitumor properties.