Establishment of an in vitro model for cisplatin resistance in human neuroblastoma cell lines

Two unique cisplatin-resistant neuroblastoma (NB) cell lines have been derived from the established lines IMR-32 and SK-N-SH by treatment with escalating doses of cisplatin. IMR/CP.20 was 6.6-fold and SK/CP.15 was 3.8-fold more resistant to the cytotoxic effects of cisplatin than the parent lines. The parent SK-N-SH cells were 16.6-fold more resistant to the effects of cisplatin than IMR-32 cells. The cisplatin-resistant cell lines demonstrated alterations to their morphology, but there was no change in the cell growth characteristics of the resistant compared to the sensitive lines. Cytogenetic analysis revealed that clonal selection of parental subclones had occurred with additional chromosomal changes in both resistant lines. Both IMR/CP.20 and SK/CP.15 lines were cross-resistant to aphidicolin and to L-phenylalanine mustard. The IMR/CP.20 line was 7.3-fold more resistant to mitomycin C than the parent line. Neither cisplatin-resistant NB line was cross-resistant to 5-fluorouracil, etoposide or doxorubicin. All NB lines had low levels of DNA repair compared to HeLa or CHO-K1 cells. However, the IMR/CP.20 cell line showed a significantly higher ability to effect DNA repair than the parent IMR-32 line, indicating that the increased resistance to cisplatin observed in this line may, in part, be due to an enhanced DNA repair capacity.