Effect of sampling time on chromosome aberration yield for 7 chemicals in Chinese hamster ovary cells.
Choice of harvest time is one of the most important variables in the assessment of whether a compound is clastogenic and in establishing a dose relation. We examined the effects of sampling time on aberration yield for 7 diverse chemicals in CHO-WBL cells by harvesting at intervals from 9 to 30 h after treatment for 3 h with or without S9 metabolic activation. We observed both the percentage of aberrant cells and the total number of aberrations. Our data suggest that for most compounds a single harvest time approximately 17-21 h after the beginning of a 3-h treatment is optimal for aberration detection in CHO cells. Maximal aberration yields were observed for 2,4-diaminotoluene, 2,6-diaminotoluene and cytosine beta-D-arabinofuranoside from 17 to 21 h, eugenol from 15 to 21 h, cadmium sulfate from 15 to 24 h and 2-aminobiphenyl, from 17 to 24 h. For adriamycin at 1 microM, the % aberrant cells remained elevated throughout the period from 9 to 29 h, while small increases at 0.1 microM ADR were found only at 13 and at 25 h. For most chemicals the maximal aberration yield occurred at a different time for each concentration tested. However, the use of 3 or more closely spaced concentrations, carefully selected to yield up to 50% toxicity, allowed detection of a positive response at a single harvest time for all 7 chemicals.
Merck Sharp and Dohme Research Laboratories, West Point, PA 19486.
C L
CL
Bean
M J
MJ
Armstrong
S M
SM
Galloway
D000611:Aminobiphenyl Compounds / Q000633:toxicity; D000818:Animals; D016466:CHO Cells; D002104:Cadmium / Q000633:toxicity; D019187:Cadmium Compounds; D002452:Cell Count; D002869:Chromosome Aberrations; D006224:Cricetinae; D003561:Cytarabine / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D005054:Eugenol / Q000633:toxicity; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D010655:Phenylenediamines / Q000633:toxicity; D013431:Sulfates; D013997:Time Factors
D000611:Aminobiphenyl Compounds; D019187:Cadmium Compounds; D009153:Mutagens; D010655:Phenylenediamines; D013431:Sulfates; D002104:Cadmium; D003561:Cytarabine; D005054:Eugenol; D004317:Doxorubicin; C014970:2-aminodiphenyl; C037123:cadmium sulfate; C025235:2,6-diaminotoluene; C010914:2,4-diaminotoluene