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Streptozotocin‐induced toxicity in CHO‐9 and V79 cells
Author(s) -
Capucci M. S.,
Hoffmann M. E.,
De Groot A.,
Natarajan A. T.
Publication year - 1995
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850260111
Subject(s) - chinese hamster ovary cell , cell cycle , streptozotocin , cell culture , chinese hamster , microbiology and biotechnology , dna damage , cell , biology , cytotoxicity , dna , cell cycle checkpoint , biochemistry , in vitro , genetics , endocrinology , diabetes mellitus
The cytotoxicity of streptozotocin (STZ) was investigated in Chinese hamster fibroblast lines (CHO‐9 and V79) in comparison to two other alkylating agents, methylnitrosourea (MNU) and ethylnitro‐sourea (ENU), using cell survival as the endpoint. It was found that V79 cells were far more resistant to methylation induced by STZ and MNU than CHO‐9 cells (20 and four times, respectively) but equally sensitive to the ethylating agent ENU. The extent of STZ‐induced DNA methylation was estimated by analyzing the extent of O 6 ‐metG and N7‐metG adducts in the DNA of treated cells through high‐performance liquid chromatography (HPLC) with electrochemical detection. The number of adducts as well the efficiencies of their removal from the DNA were similar in both cell lines. The response of these cells to the presence of DNA damage was evaluated by analysis of STZ effects on DNA replication and cell cycle progression. Measurement of [ 3 H]‐thymidine incorporation showed a similar pattern of response at the level of inhibition of DNA synthesis in both cell lines. However, analysis of meta‐phase cells 36 hr after STZ exposure showed an accumulation of cells in the second cycle in the CHO‐9 line, indicating induction of a cell cycle arrest. Only a slight effect was observed on cell cycle progression in V79 cells, indicating that the methylation resistance of these cells could be related to their ability to progress through the cell cycle despite the presence of DNA lesions. © 1995 Wiley‐Liss, Inc.