In19  A very interesting and stimulating review on sunscreens

From: Dr. Dietrich Averbeck
Date: 12/11/97
Time: 4:54:26 PM
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As always you are right on the spot where photobiology is expected to provide a better understanding of matters related to human health. In fact, your review is actually very interesting. It gives a quick overview of the subject and provides very stimulating thoughts for what is and can be done in the field to prove that compounds (in your case sunscreens) are photoprotective and non photogenotoxic. With regard to test designs in this domain and from my point of view, it would be important to stress the importance of using light sources emitting a well-defined physiologically relevant sunlight spectrum. Furthermore, since we know much more about the behaviour of human melanocytes than of fish, it should be pointed out that human melanocytes should represent an even more adequate system permitting extrapolation to what happens in humans after solar irradiation. On page 5 you sum up a few statements concerning possible short-term tests for predicting long-term photogenotoxic effects. To add also to this discussion, as a yeast geneticist and photobiologist, I would like to add mutagenicity testing in the yeast Saccharomyces cerevisiae as a useful complement in general genotoxicity (see for review, Moustacchi et al. 1986) and, especially, in photogenotoxicity testing. In fact, Saccharomyces cerevisiae is one of the best known eukaryotic organisms due to the recent complete sequencing of the yeast genome ( > 6000 genes) (Goffeau et al. 1995). It is well characterized in terms of molecular and classic genetics. Many genetically well-defined mutants of specific cellular metabolic pathways, DNA repair and intracellular signalling are available. Strong homologies exist between yeast and human genes (in particular those concerning DNA repair and cancer predisposition (Wood 1997, Sarasin 1994, Hoejmakers 1995, Kolodner 1995). This makes yeast a very pertinent eukaryotic model and very reliable as a predictive test organism for genotoxic activity. Yeast has been already shown useful for photogenotoxicity testing (Chetelat et al. 1993) since it can withstand quite long exposures to UVB, UVA, solar simulated or solar radiation (Averbeck et al. 1990, Moysan et al. 1993). It is thus ideal for testing reciprocity between light exposure (fluence) and drug concentration and to test photosensitizing or photoprotective agents under conditions of actual use (Averbeck et al. 1989, 1990, Moysan et al. 1993). As conditional anaerobic organism photogenotoxicity can be tested in yeast in the presence and absence of oxygen (Averbeck et al. 1990). This is especially important in tests for possible photogenotoxic side effects due to oxygen-dependent (photodynamic) damage or to damage from activated oxygen species (due to oxidative metabolism, photooxidative activation or degradation). References: Averbeck, D., S. Averbeck, J. Blais, A. Moysan, G. Hüppe, P. Morlière, P. Prognon, P. Vigny and L. Dubertret (1989) Suction blister fluid: its use for pharmacodynamic and toxicologiocal studies of drugs and metabolites in vivo in human skin after topical or systemic administration. In « Models in Dermatology » Eds. H.I. Maibach and N.J. Lowe, Basel, Karger, vol. 4, pp.5-11

Averbeck, D., S. Averbeck, L. Dubertret, A.R. Young and P. Morlière (1990) Genotoxicity of bergapten and bergamot oil in Saccharomyces cerevisiae. J. Photochem. Photobiol., Part B, 7, 209-230.

Chetelat A., S. Albertini, J.H. Dresp, R. Strobel and E. Gocke (1993) Photomutagenesis test development: I. 8-Methoxypsoralen, chlorpromazine and sunscreen compounds in bacterial and yeast assays. Mutat. Res. 292, 241-250

Goffeau, A., B.G. Barrell, H. Bussey, R.W. Davis, B. Dujon, H. Feldmann, F. Galibert, J.D. Hoheisel, C. Jacq, M. Johnston, E.J. Louis, H.W. Mewes, Y. Murakami, P. Philippsen, H. Tettelin and S.G. Oliver (1996) Life with 6000 Genes. Science 274, 546- 567.

Hoeijmakers, J.H.J. (1995) Nucleotide excision repair II: from yeast to mammals, Trends in Genetics 9, 211-217

Kolodner, R.D. (1995) Mismatch repair: mechanisms and relationship to cancer susceptibility, TIBS 20, 397-401

Moustacchi, E., A. Carere, G. Morpurgo, C. Ramel and F.E. Würgler (1986) Report 11: Assays for genetic changes in fungi. In »Long-term and short-term assays for carcinogens: a critical appraisal, Eds. R. Montesano, H. Bartsch, H. Vainio, J. Wilbourn and H. Yamasaki, IARC scientific Publ. No° 83, Lyon, pp. 303-349.

Moysan, A. , P. Morlière, D. Averbeck and L. Dubertret (1993) Evaluation of phototoxic and photogenotoxic risk associated with the use of photosensitizers in suntan preparations: application to tanning preparations containing bergamot oil. Skin Parmacology 6, 282-291

Sarasin, A. (1994) Les gènes humains de la réparation de l’ADN. Médecine/sciences 10, 43-54

Wood, R.D. (1997) Nucleotide excision repair in mammalian cells. J. Biol. Chem. 272, 23465-23468

Furthermore, you might want to add in the discussion on page 7 last paragraph) a comment to the recent paper by Wayne G. Wamer, Jun-Jie Yin and Rong Rong Wei (1997) Oxidative damage to nucleic acids photosensitized by titanium dioxide. Free Radical Biology & Medicine 23, 851-858. Following your discussion it should be useful to point out that some general principles in photosensitization (importance of the localisation of the photosensitizer inside the cell, question what type of cellular components can be reached and affected and whether cellular DNA, so far the only known target for genotoxicity, can be damaged or not. In this respect the compound TiO2 might represent an interesting case. Apparently, it shows photosensitizing potential, is able to affect lipids, proteins and RNA but is unable to reach DNA in cells and thus unable to exert long term photogenotoxic effects. With best regards, Dietrich

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