Evaluation of DNA adduction of AZT in peripheral blood leukocytes of HIV-infected individuals by (32)P-post-labeling thin-layer chromatography: a feasibility study.
3'-Azido-3'-deoxythymidine (AZT, Zidovudine) has been effectively used for HIV infection treatment. It inhibits virus reproduction through viral reverse transcriptase inhibition. However, the side effects of this anti-retroviral drug might be cumulative, particularly in its effects on the patients' DNA. As a nucleoside analogue, AZT might incorporate into hosts' DNA, and then form DNA adducts. This may result in potential long-term risks of mutagenesis in AIDS patients who received therapy. In this feasibility study, a (32)P-post-labeling thin-layer chromatography (TLC) assay is successfully used to measure AZT-DNA analogue and adducts formed in peripheral blood leukocytes of AZT treated patients. There are DNA analogue/adducts measured in all four AZT treated patients' DNA specimens. This assay is reliable with the significant coefficient of correlation in both intra-assay (r = 0.8761, P = 0.0001) and inter-assay (r = 0.8761, P = 0.0001).
Huang
Jerry M
JM
Novartis Pharmaceuticals Corporation, One Health Plaza, 122-S337, East Hanover, NJ 07936, USA.
Anastos
Kathryn
K
Robison
Esther
E
Shi
Ruijin
R
Freeman
Kathy
K
Strickler
Howard
H
Steinberg
J J
JJ
D000818:Animals; D001345:Autoradiography; D002417:Cattle; D002855:Chromatography, Thin Layer; D018736:DNA Adducts / Q000032:analysis / Q000187:drug effects*; D016172:DNA Fingerprinting; D004260:DNA Repair / Q000187:drug effects; D003720:Densitometry; D005240:Feasibility Studies; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling; D007834:Lasers; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D015215:Zidovudine / Q000494:pharmacology*
D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D015215:Zidovudine