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- Title
Circadian Variation of Topoisomerase II-a in Human Rectal Crypt Epithelium: Implications for Reduction of Toxicity of Chemotherapy.
- Authors
Clayton, Frederic; Tessnow, Kathryn A.; Fang, John C.; Holden, Joseph A.; Moore, John G.
- Abstract
Topoisomerase II-alpha is a target of common chemotherapeutic agents such as doxorubicin and etoposide, which induce DNA damage by altering the activity of this enzyme. We took rectal biopsies at 4-hour intervals over a 24-hour period (seven total) from each of 10 healthy volunteers and examined immunoperoxidase-stained coded anti-topoisomerase II-alpha-stained sections. A significant circadian periodicity was seen in the number of rectal crypt epithelial cell nuclei that were stained (P = .01). Mean peak staining was at 7:23 a.m. ± 45 minutes, and the mean rate of change (difference between peak and trough expression) was 40%. Topoisomerase II-alpha expression in rectal epithelium has a significant circadian variation similar to that of tritiated thymidine incorporation. Although direct confirmation is needed, giving topoisomerase II-targeted chemotherapeutic agents at the proper time of day might reduce their mucositis side effects.
- Subjects
CIRCADIAN rhythms; DNA topoisomerase II; RECTAL cancer; DRUG therapy; EPITHELIUM; TISSUES
- Publication
Modern Pathology, 2002, Vol 15, Issue 11, p1191
- ISSN
0893-3952
- Publication type
Article
- DOI
10.1097/01.MP.0000032529.68297.B2