Changes in the frequency of chromosome aberrations in the bone marrow of mice examined at various intervals after single-dose and continual exposures to cyclophosphamide.

Cyclophosphamide was used as a model mutagen to study changes in the frequency of chromosome aberrations in mice, depending on the route of administration (intraperitoneal and intragastric), length of exposure (single-dose application and continual exposure to CY in drinking water) and after-exposure time of bone marrow slide processing. In the single-dose experiment, CY was given in the dose of 50 mg/kg by the intraperitoneal route or intragastric exposure and its effect was studied after 6, 12, 18, 24, 36, 48, 60, 72 and 96 h, analysing a total of 5 350 metaphases in 20 groups of animals. The highest frequency of aberrant cells (AB.C.) was observed after 12 and 18 h (intraperitoneal injection: 31.2 and 29.5% of AB.C., intragastric treatment: 20.4 and 21.0% of AB.C., respectively); at the same time intervals the mitotic index was significantly decreased. CY in drinking water was applied in a concentration of 0.02% and the length of exposure was 5 and 28 days. The frequency of chromosome aberrations was analysed 0, 6, 12, 24, 48 and 72 h after termination of exposure, examining a total of 13 groups and 3 750 metaphases. The highest frequency of AB.C. was detected 0--12 h after CY exposure termination (5-day exposure: 16.8--19.6% of AB.C.; 28-day exposure: 16.4--19.2% of AB.C.). The mitotic index, calculated as the number of mitoses in 500 nuclei per mouse, was not found to correlate with the frequency of aberrant bone marrow cells. On the basis of these results with a continual exposure to mutagen it seems advisable in such studies to expose mice only for 5 days and process bone marrow for cytogenetic analysis within 0--6 h after exposure termination.