Genotoxicity of [1H]benz[de]isoquinoline-1,3[2H]dione,5 amino-2-,[2-dimethylamino) ethyl] (BIDA) in human lymphocytes.
We have investigated the genotoxicity of BIDA in cultured human lymphocytes. Lymphocytes were cultured and stimulated with phytohemagglutinin (PHA) for 72 h. Doses of 0.1, 0.25, 0.5, 0.75, and 1 microgram/ml of BIDA were added to the culture at 1 h (G2 phase), and 6 h (S/G2 phase) before harvesting. Cells were harvested at the end of the 72-h culture period with 1-h colcemid treatment to accumulate mitosis, and further prepared by standard cytogenetic technique. BIDA induced chromatic type breakages and chromatid exchanges at both 1 h and 6 h. The mean number of breakages per cell was 0, 0.1, 1.0, and 1.7 after treatment with 0.1, 0.25, and 0.75 micrograms/ml, respectively. Ai 1 microgram/ml, BIDA severely inhibited cell progression and very few mitoses were observed. At 6 h the mean number of breakages per cell was 0.3 at 0.25 microgram/ml and 1.2 at 0.5 microgram/ml. Very few cells entered mitosis at 0.75 and 1 microgram/ml. To study the effect of BIDA on cells in G0 and G1, BIDA (0.75 microgram/ml) was added for 1 h to the cultures at the beginning of culture (G0), or 24 h after (G1) culture initiation. Afterward, cells were washed and reincubated in the conditioned medium for 71 or 47 h. No chromosomal aberrations were seen in these experiments. The number of chromatid breaks was minimal (0.1 to 0.4/cell). Our study suggests that BIDA induces chromatid type aberrations during G2 and S phases. The absence of chromosome type aberrations in cells treated during G0 and G1 suggests that either BIDA has no effect on these cells or that damaged cells fail to progress through S and G2 to reach mitosis.
Savaraj
N
N
Veterans Administration Medical Center, Miami, Florida 33125.
Liang
J
J
Lu
K
K
Feun
L G
LG
Hsu
T C
TC
D000225:Adenine; D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006801:Humans; D007094:Imides; D007399:Interphase; D007546:Isoquinolines / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D009153:Mutagens; D053644:Naphthalimides; D063065:Organophosphonates; D010835:Phytohemagglutinins / Q000494:pharmacology; D012854:Sister Chromatid Exchange
D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D009153:Mutagens; D053644:Naphthalimides; D063065:Organophosphonates; D010835:Phytohemagglutinins; C037020:amonafide; D000225:Adenine