Adriamycin cardiotoxicity in vivo. Selective alterations in rat cardiac mRNAs.
Adriamycin (ADR) is an antineoplastic agent with a side-effect of dilated cardiomyopathy. The present study examined ADR-induced changes in cardiac mRNA in vivo. Sprague-Dawley female rats (300 to 400 g) received from 2 to 8 mg/kg of ADR intraperitoneally. After 1 to 6 days, rats were killed and RNA was extracted from heart or gastrocnemius muscle by acid guanidinium-phenol-chloroform extraction. RNA underwent agarose electrophoresis, transfer to nitrocellulose, and hybridization with [32P]-cDNA probes specific to mRNA coding for alpha cardiac (alpha c) actin, alpha skeletal (alpha sk) actin, beta (beta) actin, and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Results showed that alpha c actin mRNA levels in heart extracts were lowest at day 3 after injection, with a 60% decrease at 8 mg/kg ADR. beta actin and G3PD mRNAs decreased 28% and 21%, respectively. In gastrocnemius muscle extracts, both alpha sk actin and G3PD mRNAs decreased 30%. Results suggest a selective effect of ADR on depressing alpha c actin mRNA in the rat heart. Such changes may relate to clinical ADR-induced heart muscle disease.
Papoian
T
T
Department of Pathology, UCLA School of Medicine, Center for the Health Sciences.
Lewis
W
W
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000199:Actins; D003285:Contractile Proteins; D012333:RNA, Messenger; D004317:Doxorubicin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases