Detection of photogenotoxicity in skin and eye in rat with the photo comet assay.
Photosensitizing drugs increase the sensitivity of the skin and the eye toward normally harmless sunlight conditions and are known to enhance the induction of skin tumors or severe injuries to the eye. The photogenotoxicity of five common drugs (sparfloxacin, dacarbazine, chlorpromazine and 8-methoxypsoralen, promazine) was investigated in the skin as well as in the retina and cornea of Wistar rats. The compounds were administered once orally by gavage and the resulting DNA damage was analyzed in the newly developed in vivo photo comet assay. All drugs except of promazine were clearly photogenotoxic in the skin. In the cornea sparfloxacin and dacarbazine induced an increased DNA damage following irradiation. A photogenotoxic effect in the retina was observed by sparfloxacin, which is the only compound tested that absorbs wavelengths reaching the retina. The drug concentration analysis revealed that the compounds were distributed into plasma, skin and eye at concentrations, which were photogenotoxic in vitro. Additionally, histopathological analysis showed no relevant alterations or inductions of necrosis, apoptosis or inflammation in the skin or eye. In conclusion, we confirmed the photogenotoxic potential of compounds from different chemical classes in the skin. Moreover, it is the first time that photogenotoxicity has been detected in the retina and cornea in an in vivo study. Based on our results it is concluded that the photo comet assay in rat is an easy and reliable method to elucidate drug induced photogenotoxicity under conditions, which are relevant to human exposure.
Struwe
Melanie
M
Novartis Pharma AG, 4002, Basel, Switzerland. melanie.struwe@novartis.com
Greulich
Karl-Otto
KO
Junker
Ursula
U
Jean
Christian
C
Zimmer
Dieter
D
Suter
Willi
W
Plappert-Helbig
Ulla
U
D000818:Animals; D020552:Comet Assay; D003315:Cornea / Q000187:drug effects* / Q000528:radiation effects*; D005260:Female; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects*
D009153:Mutagens