Summary
Tritiated 8-methoxypsoralen was given perorally to rats in amounts corresponding to therapeutic human doses. The rats were exposed to UVA light or kept in darkness. None of the fractions (apart from 3H2O from the lens) examined changed their level of radioactivity under the influence of UVA light.
Time-radioactivity curves were recorded for the skin, lens, residual eye, and the liver. Four fractions were measured: 3H2O, soluble pool, DNA-RNA, and protein. Tritiated water appeared already 1 h after ingestion, and attained maximum value 9–24 h after ingestion, indicating the efficiency with which the liver degrades 8-MOP.
3H-8-MOP and metabolites could be detected in the soluble pool in maximum amounts 2–3 h after the administration. Pretreatment with trypsin increased the concentration of 3H-8-MOP and metabolites; the origin of this extra radioactivity was the protein fraction.
The 3H-8-MOP binding to DNA or RNA was studied by pretreatments of the homogenates with DNase or RNase followed by measurement of radioactivity in the TCA extracts. This indicated that no measurable amount of 3H-8-MOP had been bound to DNA or RNA.
We conclude that 8-MOP administered to rats in amounts corresponding to human therapeutic doses does not bind to DNA or RNA in measurable amounts either after UV-light or in darkness. The experiments have shown proteins to be the main binding site in rat organs.
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Supported by the Danish Medical Research Council, grant no. 512-3287
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Engel, P.F., Wulf, H.C. Localization of radioactivity in rat organs after oral administration of tritiated 8-methoxypsoralen in therapeutic doses. Arch Dermatol Res 273, 71–84 (1982). https://doi.org/10.1007/BF00509029
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DOI: https://doi.org/10.1007/BF00509029