Metabolic activation and cytogenetic effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) in Chinese hamster ovary cells expressing murine cytochrome P450 IA2

Mutagenesis ◽  
1991 ◽  
Vol 6 (4) ◽  
pp. 253-259 ◽  
Author(s):  
Michael H. Buonarati ◽  
James D. Tucker ◽  
Jason L. Minkler ◽  
Rebekah W. Wu ◽  
Larry H. Thompson ◽  
...  
1992 ◽  
Vol 8 (6) ◽  
pp. 369-376 ◽  
Author(s):  
David H. Blakey ◽  
Earle R. Nestmann ◽  
Janet M. Bayley ◽  
K. Laurie Maus ◽  
George R. Douglas

Toluenesulfonhydrazide (TSH) is a high volume production chemical for which there is relatively little toxicological data. In this study, the mutagenic activity of TSH was determined in the Salmonella/mammalian microsome assay and the in vitro chromosomal aberration assay using Chinese hamster ovary cells. TSH induced gene mutations both with and without metabolic activation in the Salmonella/mammalian microsome assay but that it did not induce chromosomal aberrations in Chinese hamster ovary cells. The results of this study indicate that TSH is an in vitro mutagen and should be assessed for in vivo mutagenicity.


1997 ◽  
Vol 86 (4) ◽  
pp. 918-922 ◽  
Author(s):  
Edmond I. Eger ◽  
Michael J. Laster ◽  
Richard Winegar ◽  
Christine Han ◽  
Diane Gong

Background Compound A [CF2 = C(CF3)OCH2F], a degradation product of sevoflurane [(CF3)2CHOCH2F], is a vinyl ether and may be an alkylating agent. Thus it is a potential genotoxin. Methods The capacity of compound A to produce sister chromatid exchanges was measured in Chinese hamster ovary cells with and without metabolic activation. Concentrations of 11 to 468 ppm compound A were applied for 2 h, the Chinese hamster ovary cells were incubated for a further 34 h in the presence of bromodeoxyuridine, and then colcemid was added to produce arrest in metaphase. Coded slides of cells were examined blindly, and 50 chromosome spreads were counted for each test concentration. Results The lowest concentration of compound A applied without metabolic activator (27 ppm) significantly increased (P < 0.001) sister chromatid exchanges, and increasing concentrations of compound A increased the incidence of exchanges. Metabolic activation did not increase the incidence of exchanges. Conclusions Compound A increases sister chromatid exchanges at concentrations (27 ppm) obtained in low-flow systems when sevoflurane is used at concentrations approximating minimum alveolar concentration.


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