Dermatology · Biologics, Phototherapy and Newer Dermatological Therapeutics

In PUVA therapy for psoriasis, 8-methoxypsoralen (8-MOP) acts on DNA after UVA activation. Which precise photochemical reaction is responsible for its therapeutic effect?

  • A Cyclobutane dimer formation between adjacent thymine residues
  • B Production of reactive oxygen species causing lipid peroxidation only
  • C Formation of monofunctional and bifunctional covalent adducts (crosslinks) between psoralen and pyrimidine bases in DNA
  • D Psoralen intercalates into DNA without covalent bonding, inhibiting polymerase
Correct answer: C. Formation of monofunctional and bifunctional covalent adducts (crosslinks) between psoralen and pyrimidine bases in DNA

Explanation

8-MOP intercalates into DNA and upon UVA irradiation forms monofunctional adducts (one strand) and bifunctional interstrand crosslinks between the furan ring of psoralen and pyrimidine bases (thymine). These crosslinks inhibit DNA replication in rapidly-dividing keratinocytes, reduce T-cell proliferation, and modulate cytokine production. This is distinct from UV-induced cyclobutane dimers (UVB-mediated) — psoralen crosslinks are the specific pharmacological mechanism.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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