Mouse specific-locus test for the induction of heritable gene mutations by dibromochloropropane (DBCP)

The nematocide DBCP (1,2-dibromo-3-chloropropane) produced negative results in a specific-locus test for gene-mutation induction in the germline of male (101 X C3H)F1 mice, most of which were treated with 5 daily intraperitoneal injections of 80 mg/kg (total exposure, 400 mg/kg); a few received lower exposures. For treated spermatogonial stem cells, the finding of 2 mutations among 39519 offspring--a rate almost identical to the control rate--rules out (at the 5% significance level) an induced mutation frequency greater than 2.0 times the historical control rate. From treated poststem-cell stages, no mutants were found among 6240 offspring, ruling out (at the 5% significance level) a multiple of 8.0 times the control for these cell types. A multiple rearrangement (7 chromosomes involved in 3 translocations) found in one of the mutants probably arose as a postmeiotic event not associated with the DBCP treatment. The fertility of DBCP-treated males was not disturbed, in keeping with the absence of germ-cell toxicity and dominant lethals found by other investigators in these mice, and in contrast to results in certain other species. While the treated (101 X C3H)F1 mice are Ah-responsive, other findings make it questionable whether biotransformation of DBCP to reactive intermediates is accomplished via the Ah-receptor system.     

The role of GABA in dyskinesias induced by chemical stimulation of the striatum

The gamma aminobutyric acid (GABA) antagonists picrotoxin and bicuculline were injected into the striatum of rats via chronic cannulae. Dyskinesias were produced by these drugs which could be blocked by their injection combined with GABA. The intrastriatal (i.s.) injection of a cholinergic drug, carbachol, also produced dyskinesias which were blocked by GABA. The use of i.s. injection of GABA antagonists to produce an animal model of Huntington's chorea is discussed.