Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma

Abstract

Background: Disruption of natural diurnal light cycles, such as that experienced by shift workers, is linked to enhanced cancer incidence. Several mouse models of cancer have been shown to develop more severe disease when exposed to irregular light/dark cycles, further supporting the connection between circadian disruption and increased cancer risk. Cryptochrome 2 (CRY2), a repressive component of the molecular circadian clock, facilitates the turnover of the oncoprotein c-MYC, one mechanism that may link the molecular clock to tumorigenesis. In Eμ-MYC mice, which express transgenic c-MYC in B cells and develop aggressive lymphomas and leukemia, global Cry2 deletion reduces overall survival and enhances tumor formation. Moreover, lighting conditions that mimic the disruption experienced by shift workers dampens Cry2 transcripts in peripheral tissues of C57BL/6J mice. Thus, we hypothesized that exposure to disruptive lighting conditions would enhance tumor burden in Eμ-MYC mice. Methods: We housed Eμ-MYC mice in light-tight boxes set to either the control (continuous cycles of 12-hours of the light followed by 12-hours of dark, LD12:12) or chronic jetlag (eight-hour light phase advances every two to three days, CJL) lighting conditions and assessed the impact of disrupted light cycles on overall survival and tumor formation in Eμ-MYC mice. Results: Environmental disruption of circadian rhythms did not alter tumor location, tumor growth, or overall survival in female or male Eμ-MYC mice. Conclusions: Our findings support emerging evidence that suggests the impact of circadian disruption on tumorigenesis is dependent on the origin of malignancies.