Inhibition of a specific DNA repair system and nitrosourea cytotoxicity in resistant human cancer cells.

Bernard W Futscher, K. C. Micetich, D. M. Barnes, R. I. Fisher, L. C. Erickson

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

In this report we present evidence which suggests that pretreatment of a highly nitrosourea-resistant human colon tumor cell line with non-cytotoxic doses of streptozotocin (STZ) prior to, or simultaneously with, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) exposure produces synergistic increases in cytotoxicity of several logs over the cytotoxicity produced by exposure to BCNU alone. STZ pretreatment or simultaneous treatment with BCNU allowed BCNU-induced DNA interstrand crosslinks to form in this cell line, in which BCNU alone did not induce DNA interstrand-crosslinks. Reversal of the schedule (i.e., STZ following BCNU) was less effective in producing synergistic cell kill or increased DNA interstrand crosslinking. Replacement of BCNU with fresh BCNU was not effective in producing increased cell kill and produced no observable interstrand crosslinking. Direct assays for guanine O6-DNA alkyltransferase activity confirmed that more than 75% inhibition of this important DNA repair system occurred following exposure to 2.5 mM STZ and that the inhibition was virtually complete when STZ pretreatment was combined with BCNU exposure.

Original languageEnglish (US)
Pages (from-to)65-73
Number of pages9
JournalCancer Communications
Volume1
Issue number1
StatePublished - 1989
Externally publishedYes

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Carmustine
DNA Repair
Streptozocin
Neoplasms
DNA
Guanine
Tumor Cell Line
Appointments and Schedules
Colon
Cell Line

ASJC Scopus subject areas

  • Cancer Research

Cite this

Inhibition of a specific DNA repair system and nitrosourea cytotoxicity in resistant human cancer cells. / Futscher, Bernard W; Micetich, K. C.; Barnes, D. M.; Fisher, R. I.; Erickson, L. C.

In: Cancer Communications, Vol. 1, No. 1, 1989, p. 65-73.

Research output: Contribution to journalArticle

Futscher, Bernard W ; Micetich, K. C. ; Barnes, D. M. ; Fisher, R. I. ; Erickson, L. C. / Inhibition of a specific DNA repair system and nitrosourea cytotoxicity in resistant human cancer cells. In: Cancer Communications. 1989 ; Vol. 1, No. 1. pp. 65-73.
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