Circadian variation in the susceptibility of mouse epidermis to tumour induction by methylnitrosourea

To study possible circadian differences in the sensitivity of hairless mouse epidermis to a small dose of a short-acting alkylating carcinogen, groups of animals were painted once with 0.2 mg methylnitrosourea (MNU) at 08.00, 12.00, 20.00 and 24.00 h. Other animals were painted three times at weekly...

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Bibliographic Details
Published in:Virchows Archiv. Abteilung B. Zellpathologie 1984, Vol.45 (3), p.325-329
Main Authors: Clausen, O P, Iversen, O H, Thorud, E
Format: Article
Language:English
Subjects:
Animals
Cell Cycle - drug effects
Circadian Rhythm
Disease Susceptibility
Epidermis - drug effects
Epidermis - pathology
Interphase - drug effects
Methylnitrosourea
Mice
Mice, Hairless
Nitrosourea Compounds
Skin Neoplasms - chemically induced
Skin Neoplasms - pathology
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Summary:To study possible circadian differences in the sensitivity of hairless mouse epidermis to a small dose of a short-acting alkylating carcinogen, groups of animals were painted once with 0.2 mg methylnitrosourea (MNU) at 08.00, 12.00, 20.00 and 24.00 h. Other animals were painted three times at weekly intervals at 08.00 and at 20.00 h, respectively. Significantly higher tumour yields were found in animals painted at 20.00 h (when the cell cycle progression and DNA synthesis rate are lowest, and when relatively large numbers of late G1 cells may accumulate) than at any other time point investigated. Hence a circadian variation in sensitivity to MNU in mouse epidermis is confirmed. This may be due to the variations in flux of cells through the S phase. The formation of DNA/carcinogen adducts may be facilitated at times of low flux with many cells in late G1, and fixation of these errors in DNA may take place by the subsequent increased flux through S, before repair is possible.
ISSN:0340-6075
0042-6431
DOI:10.1007/BF02889874