TY - JOUR
T1 - Chlorpromazine phototoxicity
T2 - Growth inhibition and DNA-interaction in normal human fibroblasts
AU - Ljunggren, B.
AU - Cohen, S. R.
AU - Carter, D. M.
AU - Wayne, S. I.
N1 - Funding Information:
CPZ binds to various cell constituents such as nuclear DNA [7,8], microsomes (9] and proteins (10]. The significance of this binding capacity in relation to effects in vivo remains uncertain. In cultured Chinese hamster cells, however, CPZ plus longwave ultraviolet radiation (UV-A) causes an increase in the Manuscript received December 26, 1979; accepted for publication February 26, 1980. This work was supported by the National Institutes of Health: AM21784, AG01012 and AM00511 and by grants from the Alfred Osterlund and the Anders Otto Sward Foundalions (BL). Dr. Ljunggren's present addJ·ess: DepaJtmenL of Dermatology, University of Lund, General Hospital, S-2 1401 Malmo, Sweden. Reprinl requests to: Dr. D. Martin Carter, Department of Dermatology, Yale University School of Medicine, 333 Cedar Street, New· Haven, Connecticut 06510. Abbreviations: CPX: chlorprotixene CPZ: chlorpromazine DMEM: Dulbecco's modified Eagle medium PBS: phosphate buffered saline UV -A: long-wave ultraviolet radiation
PY - 1980
Y1 - 1980
N2 - Growth was impaired in normal human skin fibroblasts following treatment with chlorpromazine and long-wave ultraviolet light (UV-A). The degree of impairment was dose dependent to chlorpromazine within the concentration range tested, 2.5-20 μg/ml, in the presence of UV-A, 1 J/cm2. Pre-irradiated chlorpromazine at a concentration of 20 μg/ml had no effect on fibroblast growth. Clorprotixene, a thioxanthrene compound structurally similar to chlorpromazine at a concentration of 10 μg/ml, was not phototoxic in this system. The effects of chlorpromazine and UV-A on fibroblast DNA were studied using the technique of zone sedimentation in alkaline sucrose. In the absence of light chlorpromazine did not affect sedimentation of DNA. After UV-A irradiation at 20° or 0°C in the presence of chlorpromazine, labeled DNA sedimented more slowly indicating that it had been reduced to smaller fragments. No evidence for interstrand DNA cross-links was found. Chlorpromazine alone or in combination with UV-A did not alter the size of the DNA. These results with cultured fibroblasts indicate that the phototoxic action of chlorpromazine at 366 nm is at least partially explained by interaction with DNA and is not due to the effects of cytotoxic photoproducts.
AB - Growth was impaired in normal human skin fibroblasts following treatment with chlorpromazine and long-wave ultraviolet light (UV-A). The degree of impairment was dose dependent to chlorpromazine within the concentration range tested, 2.5-20 μg/ml, in the presence of UV-A, 1 J/cm2. Pre-irradiated chlorpromazine at a concentration of 20 μg/ml had no effect on fibroblast growth. Clorprotixene, a thioxanthrene compound structurally similar to chlorpromazine at a concentration of 10 μg/ml, was not phototoxic in this system. The effects of chlorpromazine and UV-A on fibroblast DNA were studied using the technique of zone sedimentation in alkaline sucrose. In the absence of light chlorpromazine did not affect sedimentation of DNA. After UV-A irradiation at 20° or 0°C in the presence of chlorpromazine, labeled DNA sedimented more slowly indicating that it had been reduced to smaller fragments. No evidence for interstrand DNA cross-links was found. Chlorpromazine alone or in combination with UV-A did not alter the size of the DNA. These results with cultured fibroblasts indicate that the phototoxic action of chlorpromazine at 366 nm is at least partially explained by interaction with DNA and is not due to the effects of cytotoxic photoproducts.
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U2 - 10.1111/1523-1747.ep12523279
DO - 10.1111/1523-1747.ep12523279
M3 - Article
C2 - 7410891
AN - SCOPUS:0018955101
SN - 0022-202X
VL - 75
SP - 253
EP - 256
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 3
ER -