COMPARISON OF INDUCTION OF HPRT MUTATIONS BY 1,3-BUTADIENE AND OR ITSMETABOLITES 1,2-EPOXYBUTENE AND 1,2,3,4-DIEPOXYBUTANE IN LYMPHOCYTES FROM SPLEEN OF ADULT MALE-MICE AND RATS IN-VIVO/

Induction of hprt mutations by 1,3-butadiene (ED) and its metabolites 1,2-epoxybutene (EB) and 1,2,3,4-diepoxybutane (DEB) was studied in ly mphocytes from spleens of 6- to 14-week-old mice and 10- to Ii-week-ol d rats. For unknown reasons, results from experiments with mice that r eceived inhalation exposure to ED were quite variable. In the first ex periment, mice were exposed for 5 days to 200, 500 or 1300 ppm and thi s resulted in a statistically significant, dose-dependent, induction o f mutations. When the experiment was repeated and an extra expression time for mutations was included, it was not possible to detect inducti on of mutations. In a third experiment, a 6-day exposure to 500 ppm wa s mutagenic when mice with zero mutants were not excluded from the sta tistical analysis of the data. The monofunctional metabolite EB appear ed to be mutagenic in mice (3 X 33 and 3 x 100 mg/kg), but not in rats (3 x 33 and 100 mg/kg or 30 days drinking water with 0.1, 0.3 or 1.0 mM EB). Contrary to expectations, there was no induction of mutations in mice and rats exposed to the bifunctional metabolite DEB (mice, 3 X 7, 21, 3 X 14, or 42 mg/kg; rats, 20 or 40 mg/kg or 30 days drinking water with 0.3 or 1 mM DEB), although in our earlier studies with mice and rats, DEB treatment significantly enhanced frequencies of micronu clei in splenocytes and in early spermatids of mice and rats. Some of these results differ from findings reported by other investigators. It is now becoming evident that these differences are, to a large extent , due to differences in age of the animals at the time of treatment. F or example, the mutagenic potency of ED, EB and DEB was stronger in pr eweanling mice or 4-week-old mice than in 8- to 12-week-old adult mice . (C) 1998 Elsevier Science B.V.