Mechanisms of chemical phototoxicity
Psoralens in combination with ultraviolet light (PUVA) are phototoxic and potent modulators of epidermal cell growth and differentiation. Using an in vitro cell culture model, the effects of psoralens and UVA light on the growth of epidermal cells were investigated. It was found that psoralen and UVA light interact synergistically to inhibit the growth of cells in culture. This synergism was also observed in the ability of PUVA to inhibit DNA synthesis, decrease cell survival, cause mutations and form psoralen-DNA adducts. Using a cell culture model for the differentiation of melanocytes, PUVA was also found to be a potent inducer of melanogenesis as evidenced by its ability to increase cellular tyrosinase, the enzyme responsible for melanin biosynthesis. Results from these studies indicate that PUVA can induce dramatic alterations in the growth rate and differentiation state of cells at dosage levels which are associated with minimal DNA damage. These findings are in conflict with the general assumption that the biological effects of psoralens and UVA light are associated with their ability to bind covalently to and cross-link DNA. Therefore, the author investigated the possibility that sites of action, other than DNA, are involved in the mechanism(s) by which photoactivated psoralens modulate epidermal cell growth and differentiation. The author's laboratory has found that mammalian epidermal cells contain specific, saturable, high-affinity binding sites for the psoralens that are distinct from DNA. This receptor for the psoralens, photolabeled with ({sup 3}H)-8-methoxysporalen, was visualized following sodium dodecyl sulfatepolyacrylamide gel electrophoresis. The psoralen receptor is shown to be a 22,000 dalton protein located in nonnuclear fractions of cell extracts.
- Research Organization:
- Rutgers--the State Univ., New Brunswick, NJ (USA)
- OSTI ID:
- 5733183
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMAL CELLS
ANIMAL TISSUES
ANTICOAGULANTS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
CELL DIFFERENTIATION
COUMARINS
DNA
DNA ADDUCTS
DNA REPLICATION
DRUGS
ELECTROMAGNETIC RADIATION
EPIDERMIS
EPITHELIUM
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
IN VITRO
MUTATIONS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PSORALEN
RADIATION EFFECTS
RADIATIONS
RADIOSENSITIVITY EFFECTS
SKIN
SYNERGISM
TISSUES
ULTRAVIOLET RADIATION