Expression of clock genes and xenobiotic metabolizing genes in a murine model of chronic jet jag and tumor development

ROMÁN, FERNANDA; RICHARD, SILVINA MARIEL; PALADINO, NATALIA; CERLIANI, MARÍA BELÉN; MUL FEDELE, MALENA; CHIESA, JUAN JOSÉ; AIELLO, IGNACIO; GOLOMBEK, DIEGO

Mar del Plata

Congreso; LXI Reunión Anual SAIC SAI SAFE; 2016

SAIC SAI SAFE

The circadian clock synchronizes physiological and behavioralrhythms with the daily light-dark cycle (LD). Previous studies inanimal models showed that chronic advances in the LD cycle(chronic jet lag, CJL) accelerate tumor growth. Moreover, theWorld Health Organization established that shift-work is a cancerrisk factor. Xenobiotic metabolizing genes (XMG) are responsiblefor activating and/or detoxify endo or exogenous carcinogeniccompounds. These enzymes are under circadian clock regulation.The aim was to analyze mRNA expression of Per1 andBmal1 clock genes, and XMG Nat1, Cyp1a1 and Gstt1, in thesuprachiasmatic nuclei (SCN, the central clock), and in liver andtumor tissues, using a murine model of CJL. C57BL/6 male micewere housed under the following conditions: 1)healthy animalsin LD 12:12; 2) healthy animals under CJL (6 h advances of theLD cycle every 2 days);3) animals inoculated with B16 cell line(melanoma), under LD 12:12; 4) animals inoculated with B16 cellline under CJL. Samples were taken at two time points(CT8 andCT20), from 3-6 animals/group. mRNA was quantified by qPCR,following the 2-ΔΔCt method. Results showed that CJL alter daily(LD) Bmal1expression both in SCN and liver of healthy animals.This effect was also seen in animals with tumors, for Bmal1,Per1, Gstt1 and Cyp1a1 in liver tissue, and forBmal1 in SCN.With respect to mRNA expression in tumor tissue, groups showedno differences, except for Per1 that showed significant low levelsunder CJL. On the other hand, tumor development was able todisturb Cyp1a1 circadian expression, in the liver of animals underLD 12:12; however Bmal1 displayed an expression patternsimilar to that seen in healthy animals. Data suggest that bothcentral and peripheral clocks can be disturbed by CJL, affectingthe expression of clock-controlled genes. Tumor seems not tobe able to alter the expression of clock genes, but could alterhepatic expression of XMG by other signaling pathways.