Hexachlorophene induced myelin lesions in the developing nervous system of Xenopus tadpoles: morphological and biochemical observations.

Abstract

Xenopus tadpoles were immersed in growing solution containing 0.1 or 0.2 µg of hexachlorophene (HCP) per ml for intervals up to seven days. At the higher dose, abnormalities in posture and swimming movements appeared within 8 hrs. and persisted. In vivo examination of nerve fibers in the ventral tail region after 24 hrs. revealed focal splitting and vacuolation in occasional myelin sheaths. In sections prepared for phase and electron microscopic study, similar lesions were present. They were larger and more numerous in central than peripheral myelin sheaths and were most severe in the optic nerves. Measurement by gas liquid chromatography showed that following immersion in either 0.1 or 0.2 µg HCP/ml the tadpoles absorbed 1.6–1.9 µg/g. body weight in the first 24 hrs. The levels achieved after three days in the two concentrations were 3.4 and 7.0 µg/g. body weight respectively and a level of 3.2 µg/g. was also observed after immersion in the lower concentration for seven days. The brains of tadpoles immersed in 0.2 µg HCP/ml for 1–3 days contained 2.1–2.9 µg HCP/g. wet weight. The subcellular distribution of HCP-14C was studied in pooled brains of tadpoles immersed in 0.2 µg HCP-1C/ml for 24 hrs. and six days. In addition to a pellet containing nuclei and cell debris, fractions rich in mitochondria, myelin, and microsomes were characterized by electron microscopy and chemical analyses for proteins, phospholipids, and sterols. In each case, the myelin fraction's specific radioactivity per mg protein was double that observed in other fractions. These results show that HCP can produce rapid changes in the compact lamellar structure of myelin that may be due to direct interaction with its membrane components.