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Department of Dermatology, Yale University School of Medicine [J. M. V.], New Haven, Connecticut 06510, and Chemistry Department [G. W., J. E. H.] and Biodynamics Laboratory [J. C. B.], Lawrence Berkeley Laboratories, University of California, Berkeley, Berkeley, California 94720
Cloudman (S91) murine melanoma cells were treated with 4'-hydroxymethyltrioxsalen (HMT), a bifunctional psoralen and exposed to long-wavelength (365 nm) ultraviolet light. DNA content of the cells stained with propidium iodide was measured by flow cytometry, and cell cycle phases were delineated from the DNA histograms by using a curve-fitting routine. We found that HMT in combination with long-wavelength (365 nm) ultraviolet irradiation blocked melanoma cells in different phases of the cell cycle, depending on the dose of long-wavelength (365 nm) ultraviolet light and the concentration of HMT. The binding of [3H]HMT to DNA was measured parallel with cell cycle analyses. Treatments with HMT at concentrations corresponding to about 1 HMT bound per 106 base pairs of DNA led to the accumulation of cells with predominantly G2 DNA content. At higher concentrations (2 to 3 HMT/106 base pairs), the cells were blocked in the S and G1 phases. In conclusion, we have shown that extremely sparse substitution of HMT to DNA blocks melanoma cells in the G2 phase or other phases of the cell cycle in a dose-dependent manner.
1 This Investigation was supported by Grant CA-26081 awarded by the National Cancer Institute and by the Division of Biomedical and Environmental Research, United States Department of Energy, Contract W-7405-ENG-48.
2 Recipient of Research Career Development Award 5K04 A1 00154 from USPHS, to whom requests for reprints should be addressed.
Received 6/15/81. Accepted 3/12/82.
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