This work forms part of a programme of research undertaken by the Board of the British Rubber Producers' Research Association. Our thanks are due to the Rubber ResearchInstitute of Malaya for the supplies of latex serum solids used in the investigation, to Dr A. D. Patrick for carrying out the electrophoretic analyses shown in Fig.4, and to Professor M. Stacey for permission to use the Tiselius apparatus at Birmingham University.
1. Liver microsomal preparations from chick embryos (1 day before hatching) and from 1-7 day old chicks were assayed for oxidative drug-metabolizing activity with aminopyrine, aniline and naphthalene as substrates. 2. Activities for all three substrates were highest in preparations from 1 day-old chicks. These were more than twice as active as the 7 day-old preparations and about three times as active as those from the embryos. 3. The increase in drug-metabolizing activities in newly-hatched chicks was the same for either sex and persisted for 3 days before declining towards the 7 day-old levels. 4. The developmental time-course fo the liver microsomal drug-metabolizing activities was independent of any factor in the 105 000 g supernatant fractions and of such microsomal parameters as cytochrome b5 and cytochrome P-450 content, and NADPH-cytochrome c reductase activity, but was related to changes in NADPH-cytochrome P-450 reductase levels. 5. Treatment of 7 day-old chicks with exogenous inducers, 3-methylcholanthrene or phenobarbital sodium (100 mg/kg, intraperitoneally) brought about maximal stimulation of microsomal activity as 18-24 h. The time-course of this induction was reflected by changes in microsomal cytochrome P-450 content and NADPH-cytochrome P=450 reductase activities. 6. Some induction of liver microsomal drug metabolism in 7 day-old chicks could also be brought about by injecting certain lipid-soluble egg yolk extracts.
The lifespan of mice bearing ascitic leukemia L1210 could be prolonged by treatment with (-)-emetine dihydrochloride. Optimal dosage schedules required emetine administration daily for 5 days (QD, day 1–5) or intermittently on every 4th day. (Q4D, day 1, 5, 9). Compounds related to (-)-emetine which are active in other biological systems, having the correct stereospecific structure at the C-1′ position in the molecule, a secondary amine structure at N-2′ and an ethyl-group substituent at C-3 were also effective in prolonging the survival time of L1210 leukemic mice. The effective compounds were (-)-cephaeline, (±)-2,3-dehydroemetine, (-)-2,3-dehydroemetine, (-)-tubulosine and (-)-O-methyltubulosine. In contrast, (-)-isoemetine and several derivatives of (±)-2,3-dehydroemetine, lacking the critical configuration at C-1′ or substitution at the N-2′ and C-3 positions in the molecule, were inactive in the mouse leukemia system, when administered according to the Q4D, day 1, 5, 9 schedule.
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