Application of DNA interstrand cross-link assay to estimate the sensitivity of tumor cells to alkylating agents

Fluorometric method was modified and used to detect DNA interstrand crosslinks (ISC) in tumor cells after treatment with cisplatin. Linear dose-response curve was obtained. The difference of DNA ISC formation between HeLa S3 (containing O6-methylguanine methyltransferase, Mer+) and HeLa MR (devoid of O6-methyguanine methyltransferase, Mer-) cells was studied after treatment with alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU). The survival fraction was also observed in Mer+ and Mer- cells treated with ACNU. It seems that DNA ISC formation may be used as one of the possible criteria in estimating the sensitivity of tumor cells to bifunctional alkylating agent and forecasting the efficacy of tumor chemotherapy.