Circadian variation of topoisomerase II-alpha in human rectal crypt epithelium: implications for reduction of toxicity of chemotherapy.

Department of Pathology, Salt Lake Veterans Administration Hospital, Salt Lake City, Utah 84148, USA.
Modern Pathology (Impact Factor: 6.36). 12/2002; 15(11):1191-6. DOI: 10.1097/01.MP.0000032529.68297.B2
Source: PubMed

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.

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