Abstract
The addition of different concentrations (5–20mg/dish) of allyl isopropylacetamide (AIA) and veronal (VER) to mouse liver, skin and heart tissue explant cultures increased the biosynthesis of porphyrin from endogenous precursors several-fold as compared to controls. Maximal effects were observed after a 12-hour incubation in liver culture for both AIA and VER (at 5mg drug/dish); after 2 and 6 hours in skin for AIA (10mg/dish) and VER (5mg/dish). In heart, with AIA (5mg/dish) and VER (20mg/dish), a peak was found after 2 hours, but a second increase was observed later after AIA induction. Colchicine (O.1mg/dish) did not by itself alter porphyrin biosynthesis by any tissue However, when added before or after porphyrin induction by AIA, it was able to both prevent and reverse the effect of the inducer in liver explants only, having no action whatever on other tissues or when VER was used. The usefulness of the non-animal experimental model of tissue explant cultures for investigating the porphyrinogenic properties and/or toxicity of drugs and their mechanism of action is emphasised.
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