Response of sensitive and resistant IgM immunocytomas to cis-diamminedichloroplatinum (II) does not correlate with the platination level or with the formation or removal of DNA adducts.
An IgM immunocytoma cell line sensitive to cis-diamminedichloroplatinum(II) (CDDP) and a subline with acquired resistance were grown in LOU/M rats. In a previous study with such rats that had been treated with a high dose of CDDP (10 mg/kg) the tumors did not show differences in cellular platinum content or DNA-adduct levels, either immediately after treatment or 24 h later. Recently, this high dose was found to overcome resistance. Therefore, the study was repeated with a 10-fold lower dose (1 mg/kg, i.v.). At 1 and 24 h after treatment, tumor and kidney tissue were assayed for cellular platinum (atomic absorption spectroscopy, AAS) and DNA platination (immunochemical detection of the four CDDP-DNA adducts). The results were compared with previous data. All tissues showed a linear response to dose with regard to platinum uptake as well as adduct formation, with no quantitative difference being seen between the tumors. Also the relative occurrence of the four adducts was very similar. Between 1 and 24 h, in tumors a substantial decrease occurred in both platinum content and adduct level; the kidneys showed little reduction, if any. At the lower CDDP dose a somewhat larger loss of platinum and removal of DNA adducts was observed for the resistant tumor, but these differences could be explained by "dilution", as this tumor continues to grow after low-dose treatment (about 20% within 24 h). Since the strong difference observed between the tumors in sensitivity to CDDP cannot be attributed to differences in CDDP uptake, efficiency of adduct formation, or repair capability, other mechanisms are held responsible.
Vendrik
C P
CP
Department of Oncology, University Hospital of Utrecht, The Netherlands.
Fichtinger-Schepman
A M
AM
van Dijk-Knijnenburg
W C
WC
de Jong
W H
WH
van der Minnen
A C
AC
de Groot
G
G
Berends
G F
GF
Steerenberg
P A
PA
D000818:Animals; D002945:Cisplatin / Q000378:metabolism* / Q000494:pharmacology*; D018736:DNA Adducts / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D007075:Immunoglobulin M / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009368:Neoplasm Transplantation; D051381:Rats
D018736:DNA Adducts; D007075:Immunoglobulin M; C057270:cisplatin-DNA adduct; D002945:Cisplatin