Toxicity of intracranial and intraperitoneal O6-benzyl guanine in combination with BCNU delivered locally in a mouse model View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-11

AUTHORS

Michael Guarnieri, Ann Biser-Rohrbaugh, Betty M. Tyler, Patrik Gabikian, Tracie E. Bunton, Qing Wu, Jon Weingart, Benjamin S. Carson

ABSTRACT

PURPOSE: The DNA-repair protein, O6-alkylguanine-DNA alkyl transferase, may account for resistance of CNS tumors to DNA-alkylating drugs, such as bis-(2-chloroethyl)-1-nitrosourea (BCNU). The therapeutic effects of BCNU can be potentiated by inhibiting the repair protein with an alkylated guanine analog, O6-benzyl guanine (O6BG). To investigate potential toxicity of this inhibition, we examined the effects of O6BG in mice treated with intracranial (i.c.) BCNU given via a biodegradable polymer. METHODS: Mice were treated with escalating doses of BCNU chronically delivered i.c., and with chronically delivered O6BG. The O6BG was delivered via a 7-day intraperitoneal (i.p.) or i.c. osmotic minipump. Toxicity of the combination therapies was measured from survival data. Bone marrow response was estimated from white blood cell counts. RESULTS: Combining systemic (i.p.) O6BG with locally (i.c.) delivered BCNU resulted in a decrease in the maximum tolerated dose (MTD) of local BCNU. With local delivery of O6BG, the MTD of BCNU in combination with O6BG was increased. CONCLUSIONS: Based on the results of this study, a dose escalation study will be necessary when combining systemic O6BG with the higher doses of i.c. BCNU. More... »

PAGES

392-396

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00280-002-0510-y

DOI

http://dx.doi.org/10.1007/s00280-002-0510-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042113721

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12439597


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