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June 1973, Vol 107, No. 6 >
Article | June 1973

Psoralen Plus Black Light Inhibits Epidermal DNA Synthesis

Joseph F. Walter, MD; John J. Voorhees, MD; William H. Kelsey; Elizabeth A. Duell, PhD
[+] Author Affiliations

Accepted for publication Feb 20, 1973.

Reprint requests to Department of Dermatology, University of Michigan Medical School, Ann Arbor 48104 (Dr. Walter).


Ann Arbor, Mich

From the Laboratories of the Department of Dermatology, University of Michigan Medical School, Ann Arbor.


Arch Dermatol. 1973;107(6):861-865. doi:10.1001/archderm.1973.01620210029007
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Comments

Psoralens have been used previously in an attempt to repigment vitiliginous skin. Recent reports indicate psoralens, activated by long wavelength ultraviolet light (black light), inhibit DNA synthesis in various cell types. This suggested to us a possible new therapeutic use for psoralens in proliferative epidermal diseases such as psoriasis. This study shows that trioxsalen plus black light markedly inhibits epidermal DNA synthesis. Trioxsalen or black light alone has no significant effect. Our own preliminary clinical studies show improvement of chronic plaque type psoriatic lesions in eight of 11 patients using topically applied trioxsalen and black light. We suggest that further critical clinical investigation of psoralens either topically or systemically in combination with black light for proliferative skin diseases is warranted.

REFERENCES

1 +
Lerner AB, Denton CR, Fitzpatrick TB:  Clinical and experimental studies with 8-methoxypsoralen in vitiligo . J Invest Dermatol 20: 299-314, 1953;.
2 +
Fitzpatrick TB, et al:  Hydroquinone and psoralens in the therapy of hypermelanosis and vitiligo . Arch Dermatol 93:589-600, 1966;.
3 +
Fulton JE, Leyden J, Papa C:  Treatment of vitiligo with topical methoxsalen and black light . Arch Dermatol 100:224-229, 1969;.
4 +
Epstein JH, Fukuyama K:  A study of 8-methoxypsoralen (8-MOP) induced phototoxic effects on mammalian epidermal macromolecular synthesis in vivo . J Invest Dermatol 54:350-351, 1970;.
5 +
Baden HP, et al:  DNA synthesis in normal and xeroderma pigmentosum fibroblasts following treatment with 8-methoxypsoralen and long wave ultraviolet light . Biochim Biophys Acta 262:247-255, 1972;.
6 +
Weinstein GD, Frost P:  Abnormal cell proliferation in psoriasis . J Invest Dermatol 50:254-259, 1968;.
7 +
Grube DD, Auerbach H, Brues AM:  Diurnal variation in the labelling index of mouse epidermis: A double isotope autoradiographic demonstration of changing flow rates . Cell Tissue Kinet 3:363-373, 1970;.
8 +
Voorhees JJ, et al:  Decreased cyclic AMP in the epidermis of lesions of psoriasis . Arch Dermatol 105:695-701, 1972;.
9 +
Hennings H, Elgjo K:  Epidermal regeneration after cellophane tape stripping of hairless mouse skin . Cell Tissue Kinet 3:243-252, 1970;.
10 +
Burton K:  Determination of DNA concentration with diphenylamine , in Grossman L, Moldave K (eds): Methods in Enzymology . New York, Academic Press Inc, 1968;, vol 12, pp 163-165.
11 +
Oginsky EL, et al:  Lethal photosensitization of bacteria with 8-methoxypsoralen to long wavelength ultraviolet radiation . J Bacteriol 78:821-833, 1959;.
12 +
Musajo L, et al:  Photosensitizing furocoumarins: Interaction with DNA and photo-inactivation of DNA containing viruses . Experientia 21:22-24, 1965;.
13 +
Musajo L, et al:  Photoinactivation of Ehrlich ascites tumor cells in vitro obtained with skin photosensitizing furocoumarins . Experientia 23:335-336, 1967;.
14 +
Pathak MA, Fitzpatrick TB:  Bioassay of natural and synthetic furocoumarins (psoralens) . J Invest Dermatol 32:509-518, 1959;.
15 +
Musago L, Rodighiero G:  The skin photosensitizing furocoumarins . Experientia 18:153-161, 1962;.
16 +
Toda K, et al:  Alteration of racial differences in melanosome distribution in human epidermis after exposure to ultraviolet light . Nature [New Biol] 236:143-145, 1972;.
17 +
Musajo L, Rodighiero G, Dall'Acqua F:  Evidence of a photoreaction of the photosensitizing furocoumarins with DNA and with pyrimidine nucleosides and nucleotides . Experientia 21: 24-26, 1965;.
18 +
Musajo L, Rodighiero G:  Studies on the photo-C4-cycloaddition reactions between skin photosensitizing furocoumarins and nucleic acids . Photochem Photobiol 11:27-35, 1970;.
19 +
Rodighiero G, et al:  Mechanism of skin photosensitization by furocoumarins: Photoreactivity of various furocoumarins with native DNA and with ribosomal RNA . Biochim Biophys Acta 217:40-49, 1970;.
20 +
Krämer DM, Pathak MA:  Photoaddition of psoralen and of 4,5′,8-trimethylpsoralen to DNA . Photochem Photobiol 12:333-337, 1970;.
21 +
Cole RS:  Light induced cross linking of DNA in the presence of a furocoumarin (psoralen): Studies with phage y, Escherichia coli, and mouse leukemia cells .Biochim Biophys Acta 217:30-39, 1970;.
22 +
Dall'Acqua F, et al:  Formation of interstrand cross linking in the photoreactions between furocoumarins and DNA . Z Naturforsch 26:561-569, 1971;.
23 +
Lawley PD, Brookes P:  Molecular mechanism of the cytotoxic action of difunctional alkylating agents and of resistance to this action . Nature 206:480-483, 1965;.
24 +
Trosko JE, Isoun M:  Photosensitizing effect of trisoralen on DNA synthesis in human cells grown in vitro . Int J Radiat Biol 19:87-92, 1971;.
25 +
Borden F, Baccichetti F, Musajo L:  Inhibition of nucleic acid synthesis in Ehrlich ascite tumor cells by irradiation in vitro in the presence of skin photosensitizing furocoumarins . Experientia 28:148, 1972;.
26 +
Allyn B:  Studies on photoxicity in man and laboratory animals . Read before the 21st annual meeting of the American Academy of Dermatology, Chicago, Dec 1-6, 1962 .
27 +
Tronnier H, Schüle D:  First results of therapy with long wave UV after photosensitization of skin , in Schenck GO (ed): Book of Abstracts, Symposia, and Contributed Papers, Sixth International Congress on Photobiology. Bochum, Germany, 1972 , p 340.

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1 +
Lerner AB, Denton CR, Fitzpatrick TB:  Clinical and experimental studies with 8-methoxypsoralen in vitiligo . J Invest Dermatol 20: 299-314, 1953;.
2 +
Fitzpatrick TB, et al:  Hydroquinone and psoralens in the therapy of hypermelanosis and vitiligo . Arch Dermatol 93:589-600, 1966;.
3 +
Fulton JE, Leyden J, Papa C:  Treatment of vitiligo with topical methoxsalen and black light . Arch Dermatol 100:224-229, 1969;.
4 +
Epstein JH, Fukuyama K:  A study of 8-methoxypsoralen (8-MOP) induced phototoxic effects on mammalian epidermal macromolecular synthesis in vivo . J Invest Dermatol 54:350-351, 1970;.
5 +
Baden HP, et al:  DNA synthesis in normal and xeroderma pigmentosum fibroblasts following treatment with 8-methoxypsoralen and long wave ultraviolet light . Biochim Biophys Acta 262:247-255, 1972;.
6 +
Weinstein GD, Frost P:  Abnormal cell proliferation in psoriasis . J Invest Dermatol 50:254-259, 1968;.
7 +
Grube DD, Auerbach H, Brues AM:  Diurnal variation in the labelling index of mouse epidermis: A double isotope autoradiographic demonstration of changing flow rates . Cell Tissue Kinet 3:363-373, 1970;.
8 +
Voorhees JJ, et al:  Decreased cyclic AMP in the epidermis of lesions of psoriasis . Arch Dermatol 105:695-701, 1972;.
9 +
Hennings H, Elgjo K:  Epidermal regeneration after cellophane tape stripping of hairless mouse skin . Cell Tissue Kinet 3:243-252, 1970;.
10 +
Burton K:  Determination of DNA concentration with diphenylamine , in Grossman L, Moldave K (eds): Methods in Enzymology . New York, Academic Press Inc, 1968;, vol 12, pp 163-165.
11 +
Oginsky EL, et al:  Lethal photosensitization of bacteria with 8-methoxypsoralen to long wavelength ultraviolet radiation . J Bacteriol 78:821-833, 1959;.
12 +
Musajo L, et al:  Photosensitizing furocoumarins: Interaction with DNA and photo-inactivation of DNA containing viruses . Experientia 21:22-24, 1965;.
13 +
Musajo L, et al:  Photoinactivation of Ehrlich ascites tumor cells in vitro obtained with skin photosensitizing furocoumarins . Experientia 23:335-336, 1967;.
14 +
Pathak MA, Fitzpatrick TB:  Bioassay of natural and synthetic furocoumarins (psoralens) . J Invest Dermatol 32:509-518, 1959;.
15 +
Musago L, Rodighiero G:  The skin photosensitizing furocoumarins . Experientia 18:153-161, 1962;.
16 +
Toda K, et al:  Alteration of racial differences in melanosome distribution in human epidermis after exposure to ultraviolet light . Nature [New Biol] 236:143-145, 1972;.
17 +
Musajo L, Rodighiero G, Dall'Acqua F:  Evidence of a photoreaction of the photosensitizing furocoumarins with DNA and with pyrimidine nucleosides and nucleotides . Experientia 21: 24-26, 1965;.
18 +
Musajo L, Rodighiero G:  Studies on the photo-C4-cycloaddition reactions between skin photosensitizing furocoumarins and nucleic acids . Photochem Photobiol 11:27-35, 1970;.
19 +
Rodighiero G, et al:  Mechanism of skin photosensitization by furocoumarins: Photoreactivity of various furocoumarins with native DNA and with ribosomal RNA . Biochim Biophys Acta 217:40-49, 1970;.
20 +
Krämer DM, Pathak MA:  Photoaddition of psoralen and of 4,5′,8-trimethylpsoralen to DNA . Photochem Photobiol 12:333-337, 1970;.
21 +
Cole RS:  Light induced cross linking of DNA in the presence of a furocoumarin (psoralen): Studies with phage y, Escherichia coli, and mouse leukemia cells .Biochim Biophys Acta 217:30-39, 1970;.
22 +
Dall'Acqua F, et al:  Formation of interstrand cross linking in the photoreactions between furocoumarins and DNA . Z Naturforsch 26:561-569, 1971;.
23 +
Lawley PD, Brookes P:  Molecular mechanism of the cytotoxic action of difunctional alkylating agents and of resistance to this action . Nature 206:480-483, 1965;.
24 +
Trosko JE, Isoun M:  Photosensitizing effect of trisoralen on DNA synthesis in human cells grown in vitro . Int J Radiat Biol 19:87-92, 1971;.
25 +
Borden F, Baccichetti F, Musajo L:  Inhibition of nucleic acid synthesis in Ehrlich ascite tumor cells by irradiation in vitro in the presence of skin photosensitizing furocoumarins . Experientia 28:148, 1972;.
26 +
Allyn B:  Studies on photoxicity in man and laboratory animals . Read before the 21st annual meeting of the American Academy of Dermatology, Chicago, Dec 1-6, 1962 .
27 +
Tronnier H, Schüle D:  First results of therapy with long wave UV after photosensitization of skin , in Schenck GO (ed): Book of Abstracts, Symposia, and Contributed Papers, Sixth International Congress on Photobiology. Bochum, Germany, 1972 , p 340.

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