5-Fluorouracil induces autophagic degeneration in rat oral keratinocytes.

• In this study, we investigated the effect of 5-fluorouracil (5-FU) on the keratinocytes of oral epithelium. Female Lewis rats were given 5-FU i.v. and were killed 12, 24 or 36 h after injection. The buccal mucosa was dissected. The number of nuclei with DNA strand breaks and the total number of nuclei per volume of the epithelial basal cell layer was estimated using terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling. Epithelial cells were analysed by flow cytometry, transmission electron microscopy and a dye exclusion test. The number of cells with DNA strand breaks increased in 5-FU treated rats. Flow cytometry showed a decrease in cell size and an increase in granularity with increasing doses of 5-FU. Dye exclusion gave no indication of degenerate cell membranes. By transmission electron microscopy, the cells showed evidence of degeneration, shrinkage and loss of cell-to-cell contact. Vacuolation was extensive and, in contrast to apoptotic cells, nuclear chromatin condensation seemed to occur centrally in the nuclei. The results show that 5-FU treatment in vivo induces alterations in rat oral keratinocytes that are consistent with autophagic degeneration.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Odontologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dentistry (hsv//eng)

Keyword

Animals

Antimetabolites

Antineoplastic

pharmacology

Autophagy

Cheek

DNA Fragmentation

Female

Fluorouracil

pharmacology

In Situ Nick-End Labeling

Keratinocytes

drug effects

ultrastructure

Microscopy

Electron

Mouth Mucosa

drug effects

ultrastructure

Rats

Rats

Inbred Lew

Publication and Content Type

ref (subject category)

art (subject category)