Chromatid aberration dose responses and dispersal in human G2 lymphocytes treated with bleomycin: comparison with equivalent X-irradiation reveals formation of a novel class of heavily damaged cells.

We describe the dose responses and dispersal of chromatid (ct) aberrations in human peripheral blood lymphocytes, treated with a 5-min pulse of bleomycin (BLM) in doses ranging from 0.78 to 200 micrograms/ml during the G2 phase of the cell cycle. Damage was assessed in cells fixed at the time of peak damage 1 h after treatment. Both ct breaks and the percentages of damaged cells rose according to log BLM dose above 6.3 micrograms/ml only. Below this dose all endpoints exhibited flat responses suggestive of thresholding. A dose of 100 micrograms/ml produced similar amounts and distribution of ct breakage per cell (B/c) as a previously studied X-ray dose of 0.8 Gy, permitting future direct cytogenetic comparisons between clastogens. Within the scorable range (0-29 B/c) the dispersal of ct breakage after BLM treatment resembled that after equivalent X-irradiation; but BLM treatment alone resulted in the formation of heavily damaged cells (HDC) defined as with > or = 30 B/c, representing a cytogenetic endpoint of DNA damage reminiscent of apoptosis. At the dose producing equivalent chromatid breakage, BLM produced 7.4 times fewer exchanges than X-rays in G2.