Record Display for the EPA National Library Catalog


Main Title Cyclophosphamide Teratogenesis: Evidence for Compensatory Responses to Induced Cellular Toxicity.
Author Francis, B. M. ; Rogers, J. M. ; Sulik, K. K. ; Alles, A. J. ; Elstein, K. H. ;
CORP Author Health Effects Research Lab., Research Triangle Park, NC. Developmental Toxicology Div. ;North Carolina Univ. at Chapel Hill. ;NSI Technology Services Corp., Research Triangle Park, NC.
Publisher c1990
Year Published 1990
Report Number EPA/600/J-90/352;
Stock Number PB91-163667
Additional Subjects Cyclophosphamide ; Toxicity ; Teratogens ; Cell survival ; Flow cytometry ; Cell cycle ; Deoxyribonucleic acids ; Histology ; Fluorescence spectrometry ; Reprints ; Nile blue sulfate
Library Call Number Additional Info Location Last
NTIS  PB91-163667 Some EPA libraries have a fiche copy filed under the call number shown. 07/26/2022
Collation 12p
Cyclophosphamide (CP) administered ip to pregnant mice on day 10 of gestation causes severe malformations at 20 mg/kg and is embryolethal at higher doses. In the present study, CP was administered at 1, 5, 10 or 20 mg/kg. Embryos were removed at 8 and 28 hrs post dosing for immediate staining with Nile Blue sulfate to identify areas of cell death. Forelimb buds of other embryos were removed for flow cytometric analyses. Additional litters were examined at term for malformations. Although only the highest dose produced malformations, a dose-related increase in the percentage of limb bud cells in S phase block was detectable at all doses at 8 hours post exposure and persisted through 28 hours for doses equal to or > 10 mg/kg. Nile Blue sulfate staining showed increased cell death in the limb buds 28 hours after exposure to 10 mg/kg CP, or higher. The cell death was most pronounced in areas of rapid cell proliferation. The absence of an obvious teratogenic response at dose levels that produced significant cellular toxicity indicates that a measure of embryonic damage can be repaired and/or compensated. The implications of these findings for the existence of thresholds in developmental toxicity are discussed.