DNA repair capacity and cisplatin sensitivity of human testis tumour cells.
Metastatic testicular germ cell tumours can be cured using cisplatin-based combination chemotherapy. To investigate the role of DNA repair in cisplatin sensitivity, we measured the formation and removal of cisplatin adducts in the whole genome and in specific genomic regions in 3 testis and 3 bladder cancer cell lines. Following a 1 hr exposure to 50 microM cisplatin, the mean level of DNA platination was lower in the testis tumour cell lines. During a 72 hr post-treatment incubation period, the 3 bladder cell lines removed platinum from the overall genome, whereas 2 of the testis tumour cell lines showed relatively little reduction of DNA platination. The third testis tumour cell line, SuSa, showed an intermediate capacity to remove cisplatin. Cisplatin-induced damage and repair in selected regions of the actively transcribed N-ras gene and the inactive CD3delta gene were measured using quantitative PCR. The data were in agreement with those obtained with atomic absorption spectroscopy for the whole genome, showing that the bladder lines were repair-proficient: 2 of the testis tumour cell lines showed no repair, and the third testis line, SuSa, showed an intermediate level of repair in these 2 genes. Our findings confirm that reduced capacity to repair cisplatin-damaged DNA may contribute to the hypersensitivity of testis tumour cells to DNA-damaging agents.
Köberle
B
B
Institute of Urology and Nephrology, London, UK.
Grimaldi
K A
KA
Sunters
A
A
Hartley
J A
JA
Kelland
L R
LR
Masters
J R
JR
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D018736:DNA Adducts / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018237:Germinoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D013736:Testicular Neoplasms / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
D000970:Antineoplastic Agents; D018736:DNA Adducts; D004273:DNA, Neoplasm; C057270:cisplatin-DNA adduct; D002945:Cisplatin