Cyclophosphamide-induced cytogenetic effects in mouse bone marrow and spleen cells in in vivo and in vivo/in vitro assays.
Krishna-G; Nath-J; Petersen-M; Ong-T
Teratog, Carcinog, Mutagen 1987 Jan; 7(2):183-195
The comparative cytogenetic results of in-vivo and in-vivo/in-vitro studies in mouse bone marrow and spleen cells were evaluated after treatment with varying doses of cyclophosphamide (50180) (CPA). CPA was injected intraperitoneally at dosages of 10, 20, or 40mg/kg for the sister chromatid exchange (SCE) study and at 20, 40, and 60mg/kg for the chromosomal aberration study. In-vivo assays involved preparation and analysis of cells directly from animals, while in- vivo/in-vitro assays involved cell culture prior to analysis. CPA caused dose related increases in both cytogenetic end points, SCEs and chromosomal aberrations. A significant difference in induced SCEs was noted when comparing findings of in-vivo to in-vivo/in- vitro SCE tests. A consistently higher SCE response was noted in in- vivo/in-vitro than in-vivo studies. These differences arose in part from cell culturing and nonculturing effects. While no organ difference was seen in-vivo, spleen cells were more sensitive than bone marrow in the in-vivo/in-vitro condition. When comparing the findings of the two methods, a significant difference was also noted in the number of induced aberrant cells and in induced aberrations with gaps and without gaps. Both conditions resulted in linear relationships between CPA dose and cytogenetic end point, and positive in-vivo assays were correlated with positive in-vivo/in- vitro assays. The authors conclude that these methods need further evaluation using other chemicals, species, organs, and genetic end points to determine effectiveness for human biological monitoring.
NIOSH-Author; Antineoplastic-agents; Laboratory-animals; Chromosome-damage; Biological-monitoring; Screening-methods; In-vivo-studies; Genetics; Bone-marrow; Splenic-tissue;
Author Keywords: mice; sister chromatid exchanges; chromosomal aberrations; comparative genotoxicity; animal model; primary cell culture
Teratogenesis, Carcinogenesis, and Mutagenesis