Quantitation of nuclear aberrations as a screen for agents damaging to mammary epithelium

The early nuclear damage caused by two known breast carcinogens, radiation and 7,12-dimethylbenzanthracene (DMBA), was quantitated by scoring for nuclear aberrations in mammary epithelium. Seven-week-old C57BL/6J female mice were irradiated with whole body gamma radiation or were given various doses of DMBA. The terminal end buds and ducts were separated and processed for histological preparation. The number of nuclear aberrations per 1000 cells was scored from coded slides. Animals receiving no treatment had a low level of these figures in their terminal end buds (34 +/- 7/1000 cells) but the number increased in a dose-related manner to a maximum of 161 +/- 20/1000 cells when they were treated with 8 Gy. Apoptosis in the ductal epithelium was much less frequent than in the terminal buds and the quantitation of nuclear aberrations from these structures was a less sensitive and reliable indicator of damage. DMBA and N-nitroso-N-methylurea are breast carcinogens from the polycyclic aromatic hydrocarbon and nitroso classes respectively. These chemicals cause increases in the nuclear aberration incidence in the terminal end buds but related carcinogens with different target specificities and noncarcinogens do not appear to produce such elevations. These results suggest that the quantitation of nuclear aberrations in breast epithelium might be used as a short-term, tissue-specific screen for breast carcinogens.