Induction of chromosome damage in mouse bone marrow by benzo[a]pyrene

The cytogenetic effects, in vivo, of the polycyclic hydrocarbon benzo[a]pyrene were studied in adult male mice by chromosome analysis and the micronucleus test. To establish the appropriate time for bone-marrow sampling, the interval between treatment and preparation was varied. The maximal response in the micronucleus test was found 36 h after treatment versus 30 h when chromosomal aberrations were analyzed. In the micronucleus test the lowest effective dose was 25 mg/kg, whereas a significant effect (P less than 0.001) was observed at 6.25 mg/kg when aberrations were used as the mutagenic end-point. The results show that, with single treatments and different sampling intervals applied in both tests, aberration analysis had a higher resolving power than the micronucleus test at the time of maximal response. A suitable protocol for routine application of the 2 bone-marrow tests is discussed in view of the guidelines presently under preparation in the EEC and the OECD. Arguments are presented against a sub-acute treatment regimen and for a single treatment regimen with multiple sampling intervals.