ABSTRACT
1. Benzo(a)pyrene hydroxylase (BPH) activity was measured in homogenates of fetal liver (day 18) or of whole-embryos of mice on day 9, 10 or 12 of gestation after maternal pretreatment with B(a)P on 3 consecutive days. A 3H-liberation assay with 3H-B(a)P labelled either generally or at the 6-position was used. The values obtained with the embryonic/fetal tissues were compared with those found in maternal liver. 2. Three oral doses of 17.5 mg B(a)P/kg body wt were found to just significantly induce BPH in maternal liver. An induction was observed after pretreatment with 24 mg B(a)P/kg body wt in 9-, 10- or 12-day-old whole-embryos, but the Vmax reached was only 10-20% (1% on day 9) of that of adult non-induced liver. The Km (6-hydroxylation) for all tissues tested were in the same range (600-900 nM). The induction was demonstrable in embryos at tissue levels about one order of magnitude lower than those required for induction in maternal liver. 3. Treatment with 25 mg B(a)P/kg body wt on 3 consecutive days was required to induce BPH in fetal liver on day 18 of gestation. The required B(a)P tissue concentrations were about one half of those necessary for induction in maternal liver. 4. Among a variety of other polycyclic hydrocarbons only chrysene showed an inducing potency similar to that of B(a)P in adult and fetal liver. For all compounds tested there was no correlation found in the inducing potency between adult and fetal liver (e.g. coronene).(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Aryl Hydrocarbon Hydroxylases/biosynthesis , Benzopyrene Hydroxylase/biosynthesis , Embryo, Mammalian/enzymology , Fetus/enzymology , Air Pollutants/pharmacology , Animals , Benzo(a)pyrene/metabolism , Enzyme Induction , Female , Hydroxylation , Liver/enzymology , Mice , Mice, Inbred C57BL , Polycyclic Compounds/pharmacology , Pregnancy , Smoking/metabolismABSTRACT
The distribution of radioactive material within maternal and embryonic/fetal mouse tissue was studied over a period of 2 days following a single dose of 14C-benzo(a)pyrene (B(a)P) orally on days 11, 12, 13 or 18 of pregnancy. B(a)P poorly penetrated into the embryo/fetus, and 14C-radioactivity was found in embryonic tissues at concentrations one to two orders of magnitude lower than in maternal organs. If the compound was administered for 3 consecutive days at the same dose the expected cumulation was compensated for by an accelerated elimination of the substance, which is probably due to enzyme induction.
