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Toxicol Rep
2020 Dec 24;8:38-43. doi: 10.1016/j.toxrep.2020.12.009.
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4-Methylcyclohexane methanol (MCHM) affects viability, development, and movement of Xenopus embryos.
Perfetto M
,
Kirkham SG
,
Ayers MC
,
Wei S
,
Gallagher JEG
.
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Following chemical spill disasters, it is important to estimate the effects of spilled chemicals on humans and the environment. Here we analyzed the toxicological effects of the coal cleaning chemical, 4-methylcyclohexane methanol (MCHM), which was spilled into the Elk River water supply in 2014. The viability of HEK293 T human cell line cultures and Xenopus tropicalis embryos was negatively affected, and the addition of the antioxidants alleviated toxicity with MCHM exposure. Additionally, X. tropicalis embryos suffered developmental defects as well as reversible non-responsiveness and melanization defects. The impact MCHM has on HEK293 T cells and X. tropicalis points to the importance of continued follow-up studies of this chemical.
Fig. 1. Effects of MCHM on human HEK293âT cells and Xenopus tropicalis embryos viability. A. Viability of HEK293âT cells as indicated by the MTT assay treated with an increasing amount of MCHM together with various chemicals indicated in the graph. The average and standard error are graphed. Viability in control at 0âppm of MCHM is marked with a blue dashed line. Viability in control at 10âppm of MCHM is marked with a green dashed line. Viability in control at 100âppm of MCHM is marked with an orange dashed line (Nâ=â4). B. The number of HEK293âT cells with an increasing amount of MCHM supplemented with 1âmM or 10âmM GSH. C. X. tropicalis embryos were treated with 100âppm MCHM or 100âppm MCHM supplemented with 10âmM GSH at NF stage 19 (nâ=â400 per sample, Nâ=â4). D. Stage 19 embryos untreated, treated with 1000âppm MCHM, or 1000âppm MCHM supplemented with 10âmM GSH starting at NF stage 2 (nâ=â300 per sample, Nâ=â3), the red scale bar is 2âmm; * pââ¤â0.05; ** pââ¤â0.01.
Fig. 2. Non-responsive embryos over a 60-minute incubation with MCHM. A. Stage â¼35 embryos were treated with the indicated concentration of MCHM, and responses to gentle touching were recorded as described in Materials and Methods (nâ=â250 per sample, Nâ=â5). B. Quantitation of movement with different concentrations of lidocaine benzocaine, and MCHM with concentrations indicated in ppm after one hour of incubation (nâ=â60 per sample, Nâ=â3).
Fig. 3. Developmental defects displayed by surviving embryos with MCHM, benzocaine, and lidocaine. A. Xenopus embryo morphology at the indicated stages are shown when cultured in 100 ppm MCHM at NF stage 19 (n = 400 per sample, N = 4). B. Xenopus embryo morphologies when cultured in different concentrations of MCHM. C. Xenopus embryo morphologies when cultured in different concentrations of benzocaine. D. Xenopus embryo morphologies when cultured in different concentrations of lidocaine. For B-D, n = 60 per sample, N = 3.
Figure S2 Developmental defects observed in the snai2:eGFP transgenic Xenopus tropicalis line. X. tropicalis embryos were cultured in 0, 1, and 10ppm MCHM from NF stage 2 and observed at stage 40 (n=90 per sample, N=3).
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