Mechanisms of lymphocytotoxicity induced by extracorporeal photochemotherapy for cutaneous T cell lymphoma
- Royal Melbourne Hospital, Victoria (Australia)
Extracorporeal photochemotherapy is an effective treatment for cutaneous T cell lymphoma but its mode of action is uncertain. The reduction in viability of patients' photoirradiated buffy coat lymphocytes was correlated with a 35% increase in DNA single-strand breaks and marked decreases in cellular ATP and NAD levels (to 58 and 34% of control, respectively) immediately after photoirradiation. Complementary in vitro studies were conducted with normal human peripheral blood lymphocytes using a Therakos ultraviolet A (UVA) light box. UVA light was cytotoxic on its own but was potentiated by 8-methoxysporalen. 3-aminobenzamide, a poly (ADP-ribose) synthetase inhibitor, mitigated the cytotoxic effect of ultraviolet A light in the presence of 8-methoxypsoralen in lymphocytes and reduced the amount of nucleotide depletion they caused. 10 J/cm2 of UVA light in the presence of 300 ng/ml 8-methoxypsoralen increased the poly (ADP-ribose) synthetase activity of peripheral blood lymphocytes. Exposing lymphocytes to deoxycoformycin and deoxyadenosine was found to induce biochemical and physical effects similar to those of photochemotherapy. In summary, we have shown that the lymphocytotoxic effect of extracorporeal photochemotherapy for cutaneous T cell lymphoma is apparently mediated by DNA damage, subsequent poly (ADP-ribosyl)ation and adenine nucleotide depletion. It is not known how the DNA damage and resultant biochemical effects relate to the possible immunological mechanism of extracorporeal photochemotherapy; however, it is possible that its effects can be mimicked by other DNA-damaging agents.
- OSTI ID:
- 6035994
- Journal Information:
- Journal of Clinical Investigation; (USA), Vol. 86:6; ISSN 0021-9738
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ENZYME INHIBITORS
RADIOSENSITIVITY EFFECTS
LYMPHOCYTES
BIOLOGICAL RADIATION EFFECTS
LYMPHOMAS
COMBINED THERAPY
STRAND BREAKS
RADIOINDUCTION
ADENINES
ADENOSINE
ATP
DNA
MAN
NAD
TUMOR CELLS
ULTRAVIOLET RADIATION
AMINES
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AROMATICS
AZAARENES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
COENZYMES
CONNECTIVE TISSUE CELLS
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
HETEROCYCLIC COMPOUNDS
IMMUNE SYSTEM DISEASES
LEUKOCYTES
MAMMALS
MATERIALS
NEOPLASMS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PRIMATES
PURINES
RADIATION EFFECTS
RADIATIONS
RIBOSIDES
SOMATIC CELLS
THERAPY
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture