INHIBITION OF MITOCHONDRIAL (MT) DNA SYNTHESIS BY ANTI-HUMAN IMMUNODEFICIENCY VIRUS (HIV) AND ANTICANCER DEOXYNUCLEOSIDE ANALOGS: IMPLICATION IN DELAYED TOXICITY (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

INHIBITION OF MITOCHONDRIAL (MT) DNA SYNTHESIS BY ANTI-HUMAN IMMUNODEFICIENCY VIRUS (HIV) AND ANTICANCER DEOXYNUCLEOSIDE ANALOGS: IMPLICATION IN DELAYED TOXICITY (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 32:A2524 1991. Unique Identifier : AIDSLINE ICDB/91675334
Tsai CH; Chen CH; Vazquez-Padua MA; Cheng YC; Dept. of Pharmacology, Yale Univ. Sch. of Medicine, New Haven, CT; 06510

Abstract: Deoxynucleoside analogs, such as adenine arabinoside (ara-A), 2-F-ara A,2',3'dideoxycytidine (ddC), 2',3'dideoxyinosine (ddI), and 2',3'didehydro-dideoxythymidine (D4T), were shown to exhibit delayed toxicity in clinic after continuous usage. The delayed toxicity may be due to the ability of these compounds to inhibit mt DNA synthesis in cells. Several anticancer and anti-HIV nucleosides were examined for their inhibitory potential against mt DNA synthesis in cultured CEM cells. Compounds such as ddC, ddI and D4T, which cause delayed toxicity were shown to inhibit mt DNA synthesis at a lower concentration than that which inhibits cell growth in 4 days. In contrast, 2-F-ara A, ara A and 2',3'-dideoxy azidothymidine, which were frequently shown to produce delayed toxicity, could inhibit the mt DNA synthesis and cell growth to about the same extent. Cytosine arabinoside C, which did not frequently cause delayed toxicity, did not inhibit mt DNA synthesis even at 10 times the dosage of cellular ID50. In addition, 2',3'dideoxy azidouridine did not inhibit either cell growth or mt DNA synthesis at 200 uM. These results support our hypothesis and are consistent with the demonstrated clinical limiting toxicity of these compounds.

Keywords: Antimetabolites, Antineoplastic/*PHARMACOLOGY Antiviral Agents/*PHARMACOLOGY Cell Division/DRUG EFFECTS Cell Line Didanosine/PHARMACOLOGY DNA Replication/*DRUG EFFECTS DNA, Mitochondrial/*BIOSYNTHESIS/DRUG EFFECTS Human HIV/*DRUG EFFECTS Vidarabine/PHARMACOLOGY Zalcitabine/PHARMACOLOGY Zidovudine/PHARMACOLOGY ABSTRACT
910930
M9190728

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1991. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1991. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .