Chronic Artificial Light at Night Exposure Disrupts Circadian Rhythms and Modulates P53 Gene Expression in a Rat Model of Colorectal Cancer

Background: Artificial light at night (ALAN) is an increasingly prevalent environmental exposure that disrupts circadian organization and is classified as a probable human carcinogen. Circadian disruption alters physiological rhythms and molecular pathways involved in tumor suppression, oxidative balance, and inflammation, which is associated with various health risks, including cancer. Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, yet the role of ALAN in modulating CRC progression is not fully understood. Methods: Male Wistar rats were assigned to control (12 hrs light/12 hrs dark), carcinogen- exposed (1,2-dimethylhydrazine + dextran sulfate sodium; DMH/DSS), or carcinogen plus ALAN exposure (18 hrs light/6 hrs dark; 430 lux) groups for 12 weeks, six rats per group. Circadian rhythmicity was assessed using core body temperature and Cosinor analysis. Oxidative stress markers (malondialdehyde [MDA], total antioxidant capacity [TAC]), plasma carcinoembryonic antigen (CEA), colonic P53 gene expression, and histopathological changes were evaluated. Results: ALAN exposure significantly attenuated nocturnal core body temperature, delayed the acrophase and reduced the amplitude of the temperature rhythm. Carcinogen exposure increased MDA, reduced TAC, elevated CEA, downregulated P53 expression, and induced colitis-like histological alterations. Combined exposure to carcinogens and ALAN resulted in a further increase in CEA, altered oxidative stress dynamics, significant upregulation of P53 gene expression relative to carcinogen-only animals, and progression from inflammatory pathology to dysplastic glandular changes in the colon. Conclusion: Chronic ALAN exposure disrupts circadian organization and potentiates colorectal cancer progression in the presence of carcinogenic insult. These findings provide experimental evidence that environmental light exposure acts as a disease modifier in colorectal carcinogenesis, highlighting circadian health as a potential target for cancer prevention in modern light-polluted societies.