ALTERED EXPRESSION OF RESISTANCE-ASSOCIATED GENES IN HEPATOBLASTOMA XENOGRAFTS INCORPORATED INTO MICE FOLLOWING TREATMENT WITH ADRIAMYCIN OR CISPLATIN

To study the development of drug resistance in childhood hepatoblastom a (HB) using a model closely related to in vivo conditions, we cultiva ted HE xenografts from 3 patients into mice and treated these tumors w ith either adriamycin (ADR) or cisplatin (CIS). Determination of the r elative expression levels of various resistance associated genes by a cDNA-PCR approach showed: a) Significantly enhanced MDR1 gene expressi on levels after treatment with ADR in each case. b) Significantly enha nced glutathione S-transferase mu (GST mu) gene expression levels afte r treatment with CIS in 2/3 xenografts. c) Significantly decreased lev els of topoisomerase II alpha (TOPO II alpha) in tumors of the same tw o patients after treatment with either ADR or CIS. These findings give evidence that the MDR1-, GST mu- and TOPO II alpha-gene products may contribute to drug resistance in HE.