Functional and histological bladder damage in mice after photodynamic therapy: the influence of sensitiser dose and time of administration.
The bladders of anaesthetised mice were illuminated with red laser light (630 nm) at intervals of 1 day to 4 weeks after i.p. administration of Photofrin. Light was delivered intravesically by inserting a fibre optic, with a diffusing bulb tip, into the centre of fluid filled bladders. A single light dose of 11.3 J cm-2 applies 1 day after 10 mg kg-1 Photofrin caused a severe acute response, with increased urination frequency (five to seven times control) and hematuria. Recovery was good, however, and by 10 weeks only a mild (approximately two-fold) increase in frequency remained. There was no reduction in the amount of acute bladder damage or in the rate of healing when the interval between Photofrin and light was increased from 1 to 7 days but a 2 to 3 week interval lead to a significant reduction in damage. For an interval of 4 weeks there was only a mild (less than two-fold) increase in urination frequency during the first week. A drug dose of 2.5 mg kg-1 given 1 day before illumination caused transient haematuria but no increase in urination frequency. Doses of 5, 7.5 or 10 mg kg-1 all caused photosensitisation and the amount of bladder damage was drug dose dependent. The bladder seems to be well able to recover from severe acute damage induced by PDT. Occasional incidences of pyelonephritis were seen, however, suggesting that urinary tract infection during the acute period may lead to permanent renal damage.
Division of Experimental Therapy, Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Amsterdam.
F A
FA
Stewart
Y
Y
Oussoren
D000818:Animals; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D006417:Hematuria / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D010778:Photochemotherapy / Q000009:adverse effects*; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D014554:Urination / Q000187:drug effects*
D017323:Dihematoporphyrin Ether