Page 30 - G. Cell differentiation. division. and death

[G. Cell differentiation, division, and death-20]

Treatment of mouse embryonic stem cells with fludioxonil, a

phenylpyrrole fungicide, altered cell proliferation and cardiac

differentiation

Sung-Moo Lee¹, Cho-Won Kim¹, Kyung-Chul Choi¹

¹Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University,,

Cheongju 28644, Republic of Korea

In this study, we evaluated the early developmental toxicity of fludioxonil on cardiac differentiation of mouse
embryonic stem cells (mESCs). The mESCs viability significantly decreased under 50% at 10-5 M fludioxonil, but

there was no change in cell morphology by fludioxonil (10-5-10-9 M). Then, the colony formation assay was
performed to confirm the effect of fludioxonil on cell proliferation. Cell proliferation was suppressed by 10-5 M

fludioxonil, compared to the control (0.1% DMSO) at 5 days, but it was re-increased at 10 and 15 days. To test
embryoid body (EB) formation capacity of mESCs, hanging drop assay was conducted and fludioxonil reduced the

EB size at 10-5 M. In the process of differentiation to cardiomyocytes derived from mESCs, 10-5 M fludioxonil
completely inhibited the beating ratio (the ratio of the number of contracting cells to the number of attached EBs)

of cardiomyocytes at early stage of differentiation (day 5), but the beating ratio gradually increased after 5 days at
10-5M fludioxonil. It seemed that fludioxonil delayed the differentiation of mESCs to cardiomyocytes at 10-5 M

compared to control. These results imply that fludioxonil may have a potential toxicity on the developmental process
of mESCs, especially into cardiac lineage.