Evaluation of genetic toxicity of bryostatin

OBJECTIVE:To evaluate the genetic toxicity of bryostatin.METHODS:Ames test,chromosomal aberration test of chinese hamster ovary(CHO) cell and micronucleus assay were used to investigate the genetic toxicity of bryostatin.RESULTS:The results of Ames test showed that no change in mean number of revertants per plate in TA97,TA 98,TA 100,TA 102 and TA 1535 strains were observed with or without metabolic activation of S9 at the dosages of 100, 10,1,0.1 g per plate compared to the negative control.The in vitro results of CHO cell chromosomal aberration test indicated that doses of 3.75μg/ml,1.88μg/ml and 0.94μg/ml caused statistically significant difference(P0.05) compared with negative controlsin the aberration rates of CHO cells cultured for 24 h with metabolic activation of S9,or cultured for 24 h and 48 h without the metabolic activation of S9.In vivo mice marrow micronucleus test showed that bryostatin had the inductive effect of polychromatophilic erythrocyte micronucleus formation under the dosages of 12.5,25 and 50μg/kg. Compared with negative control,the differences of those exposed to treatment were all significant(P0.01).CONCLUSION: These results indicated that bryostatin did not show genetic toxicity based on the Ames test,but could adversely affect chromosomal aberration and micronucleus formation under our experimental conditions.