Recombinant human interferon beta ser protects against zidovudine-induced genetic damage in AIDS patients.
This study was conducted to evaluate the in vivo genotoxicity of zidovudine (ZDV) in patients with Acquired Immune Deficiency Syndrome (AIDS). Patients with this disease who were non-smokers and on ZDV (1200 mg/day) as their only medication for 4 weeks to 7 months were studied. Patients with AIDS who had not received ZDV served as a negative control. Whole blood cultures were initiated by conventional methods with PHA 1:50 dilution. In addition, for each culture there was an untreated control and a recombinant interferon-beta (rIFN-beta)-treated culture. The IFN-treated cultures were exposed to 10, 100, 1000, or 10000 units of rIFN-beta for the entire incubation period. The cells were harvested at 72 h and stained with a fluorescence plus Giemsa method which permits the determination of the number of division cycles a cell has completed. One hundred metaphases from first division cells were scored from each culture for chromosome aberrations that were mainly from the chromatid-type, i.e. chromatid, chromosome, and isochromatid breaks. The frequency of breaks in the ZDV and no ZDV group was 8.29 +/- 2.65 and 0.5 +/- 0.29 per 100 cells respectively (P less than 0.05). Cultures from ZDV patients that were incubated with 100 and 1000 units of rIFN-beta, however, showed a frequency of 1.3 +/- 0.71 and 1.9 +/- 1.08 respectively, which was significantly lower than observed in the cultures not exposed to IFN (P less than 0.05). At the highest dose of rIFN-beta utilized no aberrations were detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Shafik
H M
HM
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77550.
Nokta
M A
MA
Pollard
R B
RB
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D003470:Culture Media; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015215:Zidovudine / Q000009:adverse effects*
D003470:Culture Media; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D015215:Zidovudine; D016899:Interferon-beta; D000068556:Interferon beta-1a