Modification by hyperoxia of chlorphentermine- or phentermine- induced effects on newborn rat lung morphology and metabolism.
Treatment of newborns with 20 mg/kg/day chlorphentermine orally for 1 week increased incorporation of thymidine into lung DNA without an associated change in tissue morphology or cyclic AMP levels. An increase in chlorphentermine dose to 60 mg/kg resulted in an accumulation of alveolar hypertrophic macrophages and a rise in incorporation of thymidine into lung DNA; however, cyclic AMP levels were decreased. In contrast, 20 or 60 mg/kg/day for 1 week phentermine-induced depression in the incorporation of thymidine into pulmonary DNA was accompanied by a decrease in cyclic AMP but no apparent alteration in tissue morphology. Hyperoxia did not modify the phentermine-induced changes in cyclic AMP levels and pulmonary ultrastructure. In contrast, hyperoxia altered the responsiveness of newborns to 20 mg/kg chlorphentermine as evidenced by the presence of foam cells. Data suggest that the chlorphentermine-induced increase in DNA synthesis in newborn lung seems independent of changes in cyclic AMP and tha modification of drug-induced alterations by hyperoxia may be related to the chemical structure of a compound.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002745:Chlorphentermine / Q000633:toxicity*; D000242:Cyclic AMP / Q000032:analysis; D004247:DNA / Q000096:biosynthesis; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000494:pharmacology*; D010645:Phentermine / Q000031:analogs & derivatives* / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013936:Thymidine / Q000378:metabolism
D004247:DNA; D010645:Phentermine; D000242:Cyclic AMP; D002745:Chlorphentermine; D010100:Oxygen; D013936:Thymidine