The Expression of Aphidicolin Induced Fragile Sites in Human Peripheral Blood Lymphocytes

Park, Kyung Ran; Zheng, Guo Dong

Abstract

An aphidicolin is a chemical agent which selectively inhibits DNA polymerase alpha in S phase of cell cycle. The purpose of this study is toinvestigate of chromosomal abnormalities including fragile sites induced by 0.2 microgram/ml and 0.4 ng/ml aphidicolin in lymphocyte cultures of six healthy individuals. The results were follows. 1. A significant decreasing in mitotic indexes in respect to control culture was observed with both aphidicolin concentrations used. 2. The cells showing chromosome aberrations and the total number of cytogeneticic alterations were significantly increased both aphidicolin treated cultures than control cultures. 3. The total numbers of chromosomal aberrations were increased in the concentration of 0.4 microgram/ml aphidicolin compared to 0.2 microgram/ml treated groups. 4. The most frequent type of chromosomal aberration is a gap. 5. A site showing a gap or break was defined as common fragile sites (c-fra) if it appeared more than 1% of cells analyzed and in at least three of six individuals studied with the same culture treatment. Using these criteria, 3p14, 4q12, 5p13, 6q16, 9p13, and 16q23 were induced in different proportions by different concentration of aphidicolin and four of these c-fras, 4q12, 5p13, 6q16, 9p13 have not been reported so far. This results support that aphidicolin induced fragile sites differently according to cultured cell or cultured conditions, and also suggest the mechanism that common fragile sites caused be closely related with the defect of DNA synthesis in the S phase of cell cycle.