Phototumorigenesis studies of 5-methoxypsoralen in bergamot oil: evaluation and modification of risk of human use in an albino mouse skin model.
The skin of the female hairless albino mouse (Skh 1) was used to study the enhancement of solar simulated radiation (SSR) tumorigenesis by 5-methoxypsoralen (5-MOP) in model perfumes that contain bergamot oil. This work was done in association with yeast mutagenicity studies and human skin phototoxicity studies. Analyses of time-to-onset of tumour observation with 5-MOP at 0, 5, 15 and 50 ppm show a highly significant 5-MOP dose effect and the data indicate that 5-MOP has phototumorigenic potential even at 5 ppm. The addition of 0.5% UVB and 0.5% UVA sunscreens significantly reduces the tumorigenicity associated with the vehicle (i.e. 5-MOP at 0 ppm) and 5-MOP at all concentrations. Pairwise comparisons of 5-MOP (at 5 or 15 ppm) plus sunscreens with vehicle plus sunscreens show that the sunscreens afford total protection at the lower 5-MOP concentrations. Additional studies show that a 5-6 h delay between 5-MOP application and SSR exposure defers the time-to-onset of tumours as does intermittent 5-MOP and SSR treatment. A comparison of 5-MOP at 50 ppm in bergamot oil with 5-MOP at 50 ppm prepared from pure 5-MOP crystals shows identical results, indicating that the active phototumorigenic agent in bergamot oil is 5-MOP and not other related compounds, which may be present at greater concentrations. Analyses of tumour histology at death show, in general, similar patterns of malignancy for all groups. Thus although it is possible to delay tumorigenesis by various strategies, the tumours that eventually develop are just as likely to be malignant, if not more so, when compared with non-delayed groups.
Young
A R
AR
Photobiology Unit, United Medical School Guy's, Hospital, University of London, U.K.
Walker
S L
SL
Kinley
J S
JS
Plastow
S R
SR
Averbeck
D
D
Morlière
P
P
Dubertret
L
L
D000078223:5-Methoxypsoralen; D000818:Animals; D002273:Carcinogens / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008730:Methoxsalen / Q000528:radiation effects / Q000633:toxicity*; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D010476:Perfume / Q000009:adverse effects; D010777:Photochemistry; D010938:Plant Oils / Q000528:radiation effects / Q000633:toxicity*; D011838:Radiation-Sensitizing Agents / Q000633:toxicity; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D013473:Sunscreening Agents / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects
D002273:Carcinogens; D010476:Perfume; D010938:Plant Oils; D011838:Radiation-Sensitizing Agents; D013473:Sunscreening Agents; C068336:bergamot oil; D000078223:5-Methoxypsoralen; D008730:Methoxsalen