ISSN:
1432-1335
Keywords:
Nitrosoureas
;
Nitrososemicarbazides
;
Cytotoxicity assay
;
Alkaline filter elution assay
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Five different representatives (I–V) of a new class of bifunctional alkylating agents, the 4-aroyl-1-nitrosohydrazinecarboxamides (“nitrososemicarbazides”), were evaluated for their potential interaction with DNA and for their cytotoxic activity in vitro toO 6-alkylguanine-DNA alkyltransferase-positive (Mer+) and-negative (Mer−) human cell lines. The HeLa MR cell line (Mer−) showed up to 20-fold higher sensitivity at IC50 (dose that inhibits colony formation by 50%) to agents I–V than did the HeLa S3 cell line (Mer+) in a colony-formation assay. These data were compared to those obtained by treatment of the two cell lines with carmustine, a currently used antitumor drug. In Mer+ cells comparable results to those with carmustine were obtained with compounds III, IV and V; in Mer− cells compounds I and II showed nearly the same effects as carmustine. Whether compounds I–V produce DNA strand breaks and/or DNA-protein cross-links was investigated using an alkaline filter elution technique. In this assay all compounds produced DNA single-strand breaks; no correlation could be detected between the strand breakage frequency and cytostatic, mutagenic and antitumor activity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01240139
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