CHROMATID ABERRATION DOSE RESPONSES AND DISPERSAL IN HUMAN G(2) 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) aberrat ions in human peripheral blood lymphocytes, treated with a 5-min pulse of bleomycin (BLM) in doses ranging from 0.78 to 200 mu g/ml during t he G(2) 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 p ercentages of damaged cells rose according to log BLM dose above 6.3 m u g/ml only. Below this dose an endpoints exhibited flat responses sug gestive of thresholding. A dose of 100 mu g/ml produced similar amount s and distribution of ct breakage per cell (B/c) as a previously studi ed X-ray dose of 0.8 Gy, permitting future direct cytogenetic comparis ons between clastogens. Within the scorable range (0-29 B/c) the dispe rsal of ct breakage after BLM treatment resembled that after equivalen t X-irradiation; but BLM treatment alone resulted in the formation of heavily damaged cells (HDC) defined as with greater than or equal to 3 0 B/c, representing a cytogenetic endpoint of DNA damage reminiscent o f apoptosis. At the dose producing equivalent chromatid breakage, BLM produced 7.4 times fewer exchanges than X-rays in G(2).