Effects of carmustine and lomustine on arylamine N-acetyltransferase activity and 2-aminofluorene-DNA adducts in rat glial tumor cells.
Carmustine and lomustine are nitrosourea antitumor chemotherapeutic agents which were used to determine whether or not they could affect arylamine N-acetyltransferase (NAT) activity and DNA-2-aminofluorene adducts in rat glial tumor cell line (C6 glioma). The NAT activity was measured by high preformance liquid chromatography (HPLC) assaying for the amounts of N-acetyl-2-aminofluorene (AAF) and N-acetyl-p-aminobenzoic acid (N-Ac-PABA) and remaining 2-aminofluorene (AF) and p-aminobenzoic acid (PABA). The results indicate that NAT activity in glial tumor cell cytosols and intact tumor cells were decreased by carmustine and lomustine in a dose-dependent manner. The apparent values of Km and Vmax of NAT from rat glial tumor cell also decreased after co-treatment of carmustine and lomustine in both examined cytosols and intact cells. Following exposure of glial tumor cells to the various concentrations of AF with or without co-treatment with carmustine and lomustine, DNA-AF adducts were determined by using gamma-[32p]-dATP and HPLC. The DNA-AF adducts in rat glial tumor cells were decreased by co-treatment with carmustine and lomustine. This report is the first demonstration to show carmustine and lomustine did inhibit rat glial tumor cells NAT activity and DNA-AF adduct formation.
Hung
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Department of Surgery, China Medical College and Jen-Ai Hospital, Tali, Taichung.
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism*; D002330:Carmustine / Q000494:pharmacology*; D018736:DNA Adducts / Q000378:metabolism*; D005449:Fluorenes / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D007700:Kinetics; D008130:Lomustine / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
C052668:2-aminofluorene-DNA complex; D018736:DNA Adducts; D005449:Fluorenes; D008130:Lomustine; D001191:Arylamine N-Acetyltransferase; D002330:Carmustine