You are here:
EFFECTS OF METHANOL ON EMBRYONIC MOUSE PALATE IN SERUM-FREE ORGAN CULTURE
Citation:
Abbott, B., T. Logsdon, AND T. Wilke. EFFECTS OF METHANOL ON EMBRYONIC MOUSE PALATE IN SERUM-FREE ORGAN CULTURE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/323 (NTIS PB94197134).
Description:
Methanol has widespread applications in industry and manufacturing and is under development as an automotive fuel. uman exposure tomethanol would be expected to increase as its applications expand in coming years. ethanol has been shown to be a reproductive and developmental toxicant in the rodent producing cleft palate in the CD-1 mouse. evelopmental toxicity has also been demonstrated in vitro for and mouse embryos in whole embryo culture. he present study examines the developmental toxicity of methanol in the palate using a serum-free organ culture model. estation day 12 CD-1 mouse embryos were dissected and mid-craniofacial tissues were cultured in BGJ medium at 37 degrees C for 4 days with medium changes at 24 hr intervals. ultures were exposed to methanol from 0-20 mg/ml for 6 hrs, 12 hrs, 1 or 4 days. ome cultures were exposed to ethanol for 4 days at doses ranging from 3-15 mg/ml. ll cultures were gassed with a 50% O2, 5% CO, and 45% N2 upon addition of fresh medium and prior to the addition of alcohol. ollowing organ culture the craniofacial explants were examined for effects on morphology, fusion, proliferation, and growth. ncidence and completeness of palatal fusion dec with increasing exposure. epending on the concentration and duration of methanol exposure, the medial epithelium either degenerated completely or remained intact in unfused palates and either condition would interfere with fusion. ellular proliferation appeared to be a specific and sensitive target for methanol as craniofacial tissues responded to methanol with reductions in total DNA content and reduced DNA synthesis at exposures that did not affect total protein. owever, both DNA and protein decreased with increasing exposure to methanol. ncorporation of thymidine decreased significantly after 4 day exposure and autoradiography of 3H-TdR demonstrated exposure-dependent reduction in proliferation of palatal mesenchymal cells. thanol decreased fusion score, total protein, and DNA, but 3H-TdR/DNA was not significantly changed. n general the ethanol was more potent than methanol for inhibition of protein and DNA synthesis and palatal fusion. his study demonstrated that methanol can selectively affect specific sensitive cell populations and has effects on proliferation and cell fate.