2,5-Hexanedione alters microtubule assembly I. Testicular atrophy, not nervous system toxicity, correlates with enhanced tubulin polymerization.
Toxicol Appl Pharmacol 1987 May; 88(3):370-382
The assembly and structural alterations in purified brain and testis tubulin of Charles-River-CD-rats fed either a 1 percent solution of 2,5-hexanedione (110134) (HD), or a 0.035 percent solution of 3,4- dimethyl-2,5-hexanedione (25234791) (DMHD), were analyzed. The animals were killed after 4 weeks of treatment. Brain and testis tubulins for in-vitro assembly experiments were purified using diethylaminoethyl-Sephacel. The weights of both treated groups were significantly less than those of the controls, and they both showed evidence of similar nervous system impairments. The testes of HD treated animals weighed less than those of the controls and showed several histological features indicating injury, while the testes of DMHD animals showed no significant differences to the controls. The tubulin content in brain and testis crude supernatants had not changed in either group of treated animals, compared to the controls. Purified brain and testis tubulins from HD treated rats assembled earlier and more rapidly than those from the control rats. Brain tubulins from DMHD treated rats assembled in a similar manner to those of the controls, while testis tubulin from these rats exhibited an assembly pattern intermediate to that of controls and HD treated animals. Immunoblotting with antitubulin antibodies indicated the presence of a covalently crosslinked tubulin in the brains of HD treated rats. The author concludes that microtubule assembly alterations may represent the biochemical mechanism of HD induced testicular atrophy, rather than the cause of nervous system disorders.
NIOSH-Publication; NIOSH-Grant; Reproductive-system-disorders; In-vivo-studies; Laboratory-animals; Ketones; In-vitro-studies; Neurotoxicity; Central-nervous-system-disorders; Biochemical-analysis; Histology; Cellular-structures
Pathology and Lab Medicine Div. of Biology and Medicine Brown University, Box G Providence, RI 02912
Toxicology and Applied Pharmacology
Brown University, Providence, Rhode Island