CORRELATION OF GENE-SPECIFIC DAMAGE WITH CISPLATIN BETWEEN HUMAN ADENOCARCINOMA CELLS AND PERIPHERAL-BLOOD MONONUCLEAR-CELLS ANALYZED BY POLYMERASE CHAIN REACTION-STOP ASSAY

We investigated gene-specific damage in adenocarcinoma cells, obtained from pleural effusions of 9 primary lung cancer patients, induced by incubation with cisplatin for 3 h in vitro. The 2.7 kb fragment of the hypoxanthine phosphoribosyltransferase (HPRT) gene was amplified by t he polymerase chain reaction (PCR) to quantify the DNA damage. A 7-fol d difference in the extent of gene-specific damage among the patients was observed. Mononuclear cells (MNC) were obtained from freshly isola ted blood from the same patients before they received chemotherapy. Th ese cells were also incubated with cisplatin in vitro, and PCR amplifi cation of the HPRT gene was carried out. A 4-fold variation of DNA dam age among the patients was observed. Moreover, there was a linear corr elation between the extents of the DNA damage in the tumor cells and M NCs (R(2)=0.676, P=0.0016), These results suggest that the PCR-stop as say could be used to detect interindividual variations in the extent o f gene-specific damage in both tumor cells and MNC from the same patie nts induced by cisplatin treatment. In conclusion, MNC could be used t o analyze cisplatin-induced gene-specific damage in cancer patients wh ose tumor cells are inaccessible.