Inhibitory action of benzimidazole fungicides on the in vivo incorporation of [3H]thymidine in various organs of the mouse.
The effect of benomyl on the DNA turnover in various organs of the mouse was evaluated by measuring the incorporation of [3H]thymidine 24 hr after oral administration of different doses (1.3, 2.55 and 5.1 nmol/kg body weight) of benomyl. In the thymus, spleen and testis there was a clear relationship between dose and effect, the no-observed-effect level being 1.3 mmol/kg body weight. However, in the liver and kidney there was no obvious relationship between dose and effect, the [3H]thymidine incorporation being inhibited even at the lowest dose. Equimolar amounts of the closely related fungicide carbendazim inhibited the [3H]thymidine incorporation only in the testis. The observed differences between the two compounds was not a result of different absorption rates. Whole-body autoradiography indicated a rapid absorption and a similar distribution pattern for [phenyl(U)-14C)benomyl and [phenyl(U)-14C]carbendazim. Apart from an accumulation in the retina, liver and kidney, most other organs were almost devoid of [14C]benomyl- and [14C]carbendazim-associated radioactivity.
Hellman
B
B
Department of Occupational Medicine, University Hospital, Uppsala, Sweden.
Laryea
D
D
D000818:Animals; D001345:Autoradiography; D001542:Benomyl / Q000493:pharmacokinetics / Q000633:toxicity*; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000633:toxicity*; D002219:Carbamates; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005659:Fungicides, Industrial / Q000493:pharmacokinetics / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012160:Retina / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism; D014915:Whole-Body Counting
D001562:Benzimidazoles; D002219:Carbamates; D005659:Fungicides, Industrial; D004247:DNA; C006698:carbendazim; D001542:Benomyl; D013936:Thymidine