Streptozotocin-induced toxicity in CHO-9 and V79 cells.
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 ethylnitrosourea (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 O6-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 [3H]-thymidine incorporation showed a similar pattern of response at the level of inhibition of DNA synthesis in both cell lines. However, analysis of metaphase 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.
Capucci
M S
MS
MGC Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, The Netherlands.
Hoffmann
M E
ME
De Groot
A
A
Natarajan
A T
AT
D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects / Q000302:isolation & purification; D004261:DNA Replication / Q000187:drug effects; D005038:Ethylnitrosourea / Q000633:toxicity; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D008770:Methylnitrosourea / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D013311:Streptozocin / Q000633:toxicity*; D013936:Thymidine / Q000378:metabolism
D009153:Mutagens; D013311:Streptozocin; D006147:Guanine; C008450:7-methylguanine; D008770:Methylnitrosourea; D004247:DNA; C008449:O-(6)-methylguanine; D005038:Ethylnitrosourea; D013936:Thymidine