Rat testis during 2,5-hexanedione intoxication and recovery II. Dynamics of pyrrole reactivity, tubulin content, and microtubule assembly.
Toxicol Appl Pharmacol 1988 Jan; 92(1):28-33
An investigation was made of dynamic aspects in rat testis of pyrrole reactivity, tubulin content and microtubule assembly occurring during 2,5-hexanedione (110134) (2,5-HD) exposure and recovery. Charles-River-CD-rats were administered 2,5-HD as a 1 percent solution in their drinking water for 5 weeks followed by a 17 week recovery period. Crude testis supernatants were evaluated for pyrrole content in comparison with a dimethylpyrrole (DMP) standard using Ehrlich's reagent. Tubulin as a percentage of protein in testis crude supernatants was determined by colchicine binding throughout the course of intoxication and recovery. Purified tubulin was analyzed for assembly behavior by observing the change in optical density at 350 nanometers occurring on formation of microtubules from soluble tubulin. Pyrrole content reached a level of more than 30 nanomoles (nmol) of DMP equivalents per gram of testis after 2 weeks of intoxication, and remained in the range of 20 to 25nmol of DMP for the rest of the intoxication phase, with progressive decrease during recovery. Testis tubulin content increased with germ cell loss and linear regression analysis indicated a progressive loss of tubulin with time of atrophy. Intoxication decreased the tubulin nucleation time of assembly. This decrease was evident after 2 weeks of intoxication, remained low throughout the intoxication phase, and thereafter gradually returned to normal. The author concludes that the results support the previously proposed hypothesis that altered microtubule assembly in the Sertoli cells is the basic biochemical mechanism underlying 2,5-HD induced testicular injury.
NIOSH-Publication; NIOSH-Grant; Reproductive-system-disorders; Laboratory-animals; In-vivo-studies; Ketones; Intoxicants; Testes; Proteins; Biochemistry
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