Similar chromosomal changes in cisplatin-resistant and oxaliplatin-resistant sublines of the H69 SCLC cell line are not associated with platinum resistance.
Item Type:Journal Article
Citation:Stordal, B., Peters, G. and Davey, R., Similar chromosomal changes in cisplatin-resistant and oxaliplatin-resistant sublines of the H69 SCLC cell line are not associated with platinum resistance., Genes, Chromosomes and Cancer., 45, 12, 2006, 1094 - 1105
2006 - Stordal GCC.pdf (Accepted for publication (author's copy) - Peer Reviewed) 542Kb
Small cell lung cancer (SCLC) initially responds well to DNA damaging drugs such as cisplatin, however this is transitory as resistance normally develops. To investigate whether changes in chromosomal copy number caused by platinum drug treatment contributes to platinum resistance; we have analysed H69 SCLC cells and two low-level platinum-resistant sublines, H69CIS200 and H69OX400, derived by cisplatin and oxaliplatin treatment respectively. Affymetrix 10K SNP array showed that cisplatin and oxaliplatin have independently caused similar changes including loss of segments 6q21- qter and 13pter-13q.14.11 and duplication of chromosome 21. Interestingly, despite using equally cytotoxic doses of drug in the development of the cell lines, oxaliplatin caused three times more chromosomal changes than cisplatin. The resistant cell lines lose their resistant phenotype after 3 months of drug-free culture. The revertant cell lines, denoted H69CIS200-S and H69OX400-S, were also analysed by Affymetrix array to determine if chromosomal changes associated with resistance remain after the resistant phenotype is lost. In the H69OX400-S many of the changes observed in the resistant cells were absent suggesting that they contributed to the resistant phenotype including: loss of 1q23.3-qter, 10q11.23 and 19q13.12-q13.2 and duplication of segments 6p21.2-p12.3, 16q12.1-16q13, 16q21-q23.1 and 19q12. However, out of the similar changes induced by cisplatin and oxaliplatin, both the loss of 6q21-qter and gain of 21 were still present in the H69CIS200- S and H69OX400-S cells. This suggests that cisplatin and oxaliplatin induced similar changes due to inherent vulnerabilities in the H69 cells rather than changes associated with platinum resistance.
Author: STORDAL, BRITTA KRISTINA
Type of material:Journal Article
Series/Report no:Genes, Chromosomes and Cancer.;
Availability:Full text available