Preliminary evaluation of treatment and selection conditions which affect expression of anthracycline mutagenicity in Salmonella typhimurium and a diploid human lymphoblast cell line
✍ Scribed by Harvey F. Thomas
- Book ID
- 102873625
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 769 KB
- Volume
- 7
- Category
- Article
- ISSN
- 0260-437X
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✦ Synopsis
Mutagenic potency in the AmesSalmoneZla test is an important endpoint that can be influenced by biological and technical factors. The ranking of mutagenic activity of a series of anthracyclines was measured using different conditions of exposure and mutation selection. A 20 min preincubation treatment version of the Ames test using a 0.2-2.0 pg/ml (0.36-3.60 nM/ml) dose range of each of the anthracyclines Adriamycin, Daunomycin, Carminomycin, 4'-O-methyldoxorubicin and 4demethoxydoxorubicin confirmed the order of mutagenic potency seen with the same compounds under direct plating conditions. beincubation results also confirm direct-plating results by showing the greater sensitivity of selection to His' reversion over &amguanine resistance to anthracycline mutagenicity. However, the order of mutagenic potency was changed by lengthening the preincubation treatment time to 2 h or reducing the population density of the treated cell inoculum by ten fold. These results suggest that certain treatment conditions enable the treated cells to diminish the phenotypic expression of anthracycline mutagenicity. For comparative purposes, daunomycin and Adriamycin mutagenicity in response to 0.1-0.2 nM/ml and 0.1-0.3 nM/ml dose ranges, respectively, were assessed in a human cell culture system with Cthioguanine and 5-trifluorothymidine forward mutation selection. A daunomycin dose of 0.1 nM/ml generated approximately 25-fold and 20-fold increases in mutant fraction with 6-thioguanine and 5-trifluorothymidine selections, respectively. Equivalent dosing with Adriamycin generated approximately a 4-fold increase in mutant fraction with Cthioguanine selection and little or no increase with 5-trifluothymidine selection. Maximum increase in expression of mutant fraction within the anthracycline treated populations of cells occurred with a 10 day expression time. Plating for clone forming ability on the day of treatment showed that a standard 0.1 nM/ml treatment dose reduced cloning efficiency of the daunomycin treated cells by 90% and reduced the clone forming ability of the Adriamycin treated cells by 30%.