Document 0861
 DOCN  M9650861
 TI    Clastogenic factors in plasma of HIV-1 infected patients.
 DT    9605
 AU    Fuchs J; Emerit I; Levy A; Cernajvski L; Schofer H; Milbradt R;
       Department of Dermatology, Frankfurt University Hospital,; Germany.
 SO    Free Radic Biol Med. 1995 Dec;19(6):843-8. Unique Identifier : AIDSLINE
       MED/96128480
 AB    The objective of this study was to investigate the clastogenic activity
       of plasma ultrafiltrates from HIV-1 infected patients. Clastogenic
       factors are chromosome-damaging agents with low molecular weight (<
       10,000 daltons) which cause chromosome aberrations, sister chromatid
       exchanges, DNA strand breakage, and gene mutation. They have first been
       described in the plasma of irradiated persons, but they are also found
       in hereditary breakage syndromes and chronic inflammatory diseases with
       autoimmune reactions. Their formation and their clastogenic effects are
       modulated by superoxide anion radicals. We analyzed a total of 22 HIV-1
       positive patients in comparison to 20 reference plasma samples from
       healthy HIV negative blood donors of similar age. The plasma
       ultrafiltrates (filter cutoff 10,000 daltons) from patients induced a
       statistically significant increase in chromosomal breakage in the
       cytogenetic test system (20.5 +/- 6.8 aberrations per 100 cells), while
       no increase was observed in test cultures exposed to plasma
       ultrafiltrates from healthy blood donors (6.3 +/- 2.9 aberrations per
       100 cells). The breakage values were slightly, but not significantly,
       lower in the 10 patients with more than 200 T-helper cells/ml (18 +/- 4
       aberrations per 100 cells), than in the 12 patients with less than 200
       T-helper cells/ml (22.3 +/- 7.9 aberrations per 100 cells). HIV patients
       with high clastogenic activity (induction of more than 20 aberrations
       per 100 cells, range 20 to 39) showed higher plasma levels for
       malondialdehyde than those with lower clastogenic activity (less than 20
       aberrations per 100 cells, range 12 to 18). However, the difference was
       statistically not significant. Another lipid peroxidation product,
       4-hydroxynonenal, was increased equally in both groups. There were no
       significant differences in water- and lipid-soluble plasma antioxidants
       between the low- and high-breakage group. In agreement with previous
       findings, the clastogenic effects of plasma ultrafiltrates in the test
       cultures were reduced by the antioxidant enzyme superoxide dismutase.
       The presence of clastogenic factors in the plasma of HIV patients is
       further evidence for a prooxidant state in these persons. Since
       clastogenic factor formation appears to occur at an early stage of the
       disease, it may be significant for virus release or activation, because
       of the superoxide anion stimulating effects of clastogenic factors. From
       a practical standpoint, clastogenic factors may be useful for evaluation
       of promising drugs.
 DE    Acquired Immunodeficiency Syndrome/*BLOOD/GENETICS  Adult  Anions
       Antioxidants/METABOLISM  Chromosome Aberrations  Glutathione/BLOOD
       Glutathione Peroxidase/BLOOD  Human  *HIV-1  Lymphocyte Count  Male
       Malondialdehyde/BLOOD  Mutagens/*ANALYSIS  Oxidation-Reduction
       Sulfhydryl Compounds/BLOOD  Superoxide Dismutase/PHARMACOLOGY
       Superoxides/METABOLISM  T-Lymphocytes, Helper-Inducer  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).