Abstract
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-β (rIFN-β)-treated culture. The IFN-treated cultures were exposed to 10, 100, 1000, or 10000 units of rIFN-β 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<0.05). Cultures from ZDV patients that were incubated with 100 and 1000 units of rIFN-β, 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<0.05). At the highest dose of rIFN-β utilized no aberrations were detected. It would appear, therefore, that ZDV treatment results in a significant increase in chromosomal aberrations and that cultivation of cells with rIFN-β significantly decreased the appearance of these aberrations in vitro.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 205-212 |
| Number of pages | 8 |
| Journal | Antiviral Research |
| Volume | 16 |
| Issue number | 2 |
| DOIs | |
| State | Published - 1991 |
| Externally published | Yes |
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Keywords
- AIDS
- Chromosomal damage
- Interferon beta
- ZDV
ASJC Scopus subject areas
- Virology
- Pharmacology
Cite this
Recombinant human interferon beta ser protects against zidovudine-induced genetic damage in AIDS patients. / Shafik, Hasnaa M.; Nokta, Mostafa A.; Pollard, Richard B.
In: Antiviral Research, Vol. 16, No. 2, 1991, p. 205-212.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Recombinant human interferon beta ser protects against zidovudine-induced genetic damage in AIDS patients
AU - Shafik, Hasnaa M.
AU - Nokta, Mostafa A.
AU - Pollard, Richard B
PY - 1991
Y1 - 1991
N2 - 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-β (rIFN-β)-treated culture. The IFN-treated cultures were exposed to 10, 100, 1000, or 10000 units of rIFN-β 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<0.05). Cultures from ZDV patients that were incubated with 100 and 1000 units of rIFN-β, 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<0.05). At the highest dose of rIFN-β utilized no aberrations were detected. It would appear, therefore, that ZDV treatment results in a significant increase in chromosomal aberrations and that cultivation of cells with rIFN-β significantly decreased the appearance of these aberrations in vitro.
AB - 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-β (rIFN-β)-treated culture. The IFN-treated cultures were exposed to 10, 100, 1000, or 10000 units of rIFN-β 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<0.05). Cultures from ZDV patients that were incubated with 100 and 1000 units of rIFN-β, 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<0.05). At the highest dose of rIFN-β utilized no aberrations were detected. It would appear, therefore, that ZDV treatment results in a significant increase in chromosomal aberrations and that cultivation of cells with rIFN-β significantly decreased the appearance of these aberrations in vitro.
KW - AIDS
KW - Chromosomal damage
KW - Interferon beta
KW - ZDV
UR - http://www.scopus.com/inward/record.url?scp=0025788948&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025788948&partnerID=8YFLogxK
U2 - 10.1016/0166-3542(91)90026-N
DO - 10.1016/0166-3542(91)90026-N
M3 - Article
C2 - 1799278
AN - SCOPUS:0025788948
VL - 16
SP - 205
EP - 212
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 2
ER -