vervolg furocoumarine 5

Averbeck D, Averbeck S.(1998) "DNA photodamage, repair, gene induction and genotoxicity
following exposures to 254 nm UV and 8-methoxypsoralen plus UVA in a eukaryotic cell system."
Photochem Photobiol. 68(3), 289-95. Abstract. The induction and repair of different types of
photodamage and photogenotoxicity in eukaryotic cells have been the subject of many studies.
Little is known about possible links between these phenomena and the induction of DNA
damage-inducible genes. We explored this relationship using the yeast Saccharomyces
cerevisiae, a pertinent eukaryotic model. Previous results showed that the photogenotoxic
potential of 8-methoxypsoralen (8-MOP) plus UVA is higher than that of UV (254 nm). Moreover,
the induction of the ribonucleotide reductase gene RNR2 by UV and 8-MOP plus UVA in an
RNR2-LACZ fusion strain and the formation of DNA double-strand breaks (dsb) as repair
intermediates after such treatments suggest that the latter process could involve a signal for gene induction. To further substantiate this, we measured the induction of the DNA repair gene RAD51 in RAD51-LACZ fusion strains using the dsb repair and recombination deficient mutant rad52 and the corresponding wild type, and we determined the formation of dsb by pulsed-field gel electrophoresis. After treatments, the resealing of dsb formed as repair intermediates was
impaired in the rad52 mutant. At equal doses, i.e. the same number of lesions, the induction of
the RAD51 gene by UV or 8-MOP plus UVA was significantly reduced in the rad52 mutant as
compared with the wild type. The same was true when equitoxic doses were used. Thus, the
RAD52 repair pathway appears to play an important role not only in dsb repair but also in gene
induction. Furthermore, the signaling pathways initiated by DNA damage and its processing are
somewhat linked to the photogenotoxic response.

Dardalhon M, Lin W, Nicolas A, Averbeck D. (2007) “Specific transcriptional responses induced
by 8-methoxypsoralen and UVA in yeast.” FEMS Yeast Res. 7(6), 866-78. Abstract. Treatment of
eukaryotic cells with 8-methoxypsoralen plus UVA irradiation (8-MOP/UVA) induces pyrimidine
monoadducts and interstrand crosslinks and initiates a cascade of events leading to cytotoxic,
mutagenic and carcinogenic responses. Transcriptional activation plays an important part in these responses. Our previous study in Saccharomyces cerevisiae showed that the repair of these lesions involves the transient formation of DNA double-strand breaks and the enhanced
expression of landmark DNA damage response genes such as RAD51, RNR2 and DUN1, as well
as the Mec1/Rad53 kinase signaling cascade. We have now used DNA microarrays to examine
genome-wide transcriptional changes produced after induction of 8-MOP/UVA photolesions. We
found that 128 genes were strongly induced and 29 genes strongly repressed. Modifications in
gene expression concern numerous biological processes. Compared to other genotoxic
treatments, c. 42% of the response genes were specific to 8-MOP/UVA treatment. In addition to
common DNA damage response genes and genes induced by environmental stresses, a large
fraction of 8-MOP/UVA response genes correspond to membrane-related functions.

IARC (1987) “IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 5-
Methoxypsoralen and 8-methoxypsoralen plus ultraviolet irradiation.” Suppl 7: 242-245, 1987.
Kammerau B., Klebe U., Zesch A. & Schaefer H. (1976) "Penetration, permeation and resorption
of 8-methoxypsoralen." Arch. Dermatol Res. 255, 31.

Neal JJ (1989) "Myristicin, safrole, and fagaramide as phytosynergists of xanthotoxin." J Chem
Ecol 15(1), 309-315. Abstract. The methylenedioxyphenyl-containing (MDP) inhibitors of mixedfunction oxidase detoxification enzymes, myristicin, safrole, fagaramide, and isosafrole, occur with xanthotoxin or other toxic furanocoumarins in plants of the families Umbelliferae and
Rutaceae. All four MDP compounds have a synergistic effect on the toxicity of xanthotoxin
toHeliothis zea. Myristicin also increased the phototoxicity of xanthotoxin in the presence of UV
light. The term phytosynergist is used to describe plant compounds that are present at
concentrations producing no toxic effect by themselves but have a synergistic effect on
cooccurring toxins.

Nimkulrat P., Leenutaphong V. & Sudtim S. (2005) “Phototoxicity of new psoralen-containing gels and creams versus bath PUVA.” Journal of the Medical Association of Thailand 88, 1406-1411.

Pathak M.A. (1961) "Mechanism of psoralen photosensitization and in vivo biological action
spectrum of 8-methoxypsoralen" J. Invest. Dermatol 37, 397-408.

Yuzu oil – cold pressed Citrus junos Sieb. ex Tanaka)
CAS n°: 233683-84-6.
Cropwatch summary: No data.