Abnormalities in natural light regimen as trigger of tumor growth

One of the regulators of physiological rhythm patterns in humans and animals is the change in the circadian cycle implying the day-night alternation. Exposure to light at night has been found to be directly related to serious behavioral problems, as well as to the health state and the development of malignant neoplasms. Epidemiological studies show an increased risk of breast and colon cancer in night shift workers and a reduced cancer risk found in blind women. Currently, a fairly large number of the population is exposed to light pollution (light at night). Therefore experimental studies, revealing the role of abnormalities in the natural light regime in carcinogenesis, become topical.

A specific photoperiodism is observed in Karelia: a long daylight period in the spring-summer period (the season of the“white nights”) and a short daylight period in the autumn-winter period (with day light duration of 4.5 hours). Seasonal fluctuations in illuminance as a natural abnormality in the circadian rhythm pattern, as well as light pollution as an artificially produced disturbance are considered certain modifiers of the tumor growth.

The aim of our study was a comparative investigation of the long-term effects produced by different light regimes on spontaneous carcinogenesis in female rats.

Materials and methods . The experiments were carried out in 220 in-bred female rats, initially delivered by the Research Institute of Oncology named after N.N. Petrov. All animals received standard prepared laboratory food and water with free access to them. The research work was performed in compliance with the international principles specified by the Helsinki Declaration, adhering to the guidelines for the use and care of laboratory animals in research.

The study lasted up to the natural death of the animals. To measure the illuminance in testing facilities, the F-107 luxmeter (Russia) was used. All in-bred rats aged 25 days were randomly divided into 4 groups. The first group of the female rats was exposed to a standard fixed light regime (12-hour light conditions 750 lux: 12-hour dark conditions; LD). The second group of the animals was exposed to natural light (NL), and in this case, the features of the annual photoperiodicity of the North-West of Russia were taken into account. Multiple measurements of illuminance were taken at different times of the day and night within the annual cycle. Illuminance in the test room changed during the day, and its values at the level of the cells were recorded to be 50-200 lux per m2 in the morning, up to 1000 lux in the afternoon on a clear day and 500 lux on a cloudy day, and 150 to 500 lux per m2 in the evening. The third group was kept under constant illuminance (750 lux; LL) 24 hours a day. The females of the fourth group were under the conditions of day light deprivation (DD), while the illuminance in the room was 0–0.5 lux per m2. Animals dying during the experiment were dissected. All internal organs were examined during autopsy. Neoplasms were classified according to the IARC recommendations as fatal or incidental. All tumors and major internal organs suspected of the tumor growth were examined microscopically after the standard histological processing. The histological classification of the tumors proposed by the IARC was applied.

Results . Abnormalities in the natural light regime produced a statistically significant modifying effect on the development of spontaneous tumors in the female rats. So, in the NL group of rats, the incidence of neoplasms significantly increased compared to the LD group, mainly due to a double increase in the incidence of benign breast tumors. It should be noted that three cases of uterine adenocarcinoma were revealed in the NL group, while in the LD group no such tumors were observed. Housing of the female rats under the DD conditions significantly suppressed the development of all tumors, and mainly the breast tumors, compared to the reference cases. The NL and LL regimens promoted the development of all or malignant tumors only, while the DD regimen suppressed spontaneous carcinogenesis in the female rats. In the long-rank test, the differences 45 Cardiometry, Issue 24, November 2022

between the curves of the dynamics of the development of all or only malignant tumors between the reference and all other groups were highly significant (p<0.001). The highest index of tumor multiplicity (the number of tumors per tumor-bearing rat) of 1.63 was recorded in the LL group, and the lowest index of 1.07 was reported to be in the DD group. Fatal malignant neoplasms most often developed in rats in the NL regimen, least often they were found in the DD regimen. The most common neoplasms were benign tumors, accounting for 81.8% of all neoplasms. Among them, fibromas and fibroadenomas of the breast prevailed (53.8% of all tumors). The second largest group of the benign neoplasms included glandular-fibrous polyps, fibromas and uterine fibromyomas (14.4% of all tumors). Among the malignant tumors, which accounted for 18.8% of all neoplasms, hemoblastoses, carcinomas of internal organs and sarcomas were approximately equally shared (37.5; 37.5 and 25%, respectively). Malignant mesenchymal tumors were represented by poorly differentiated sarcomas located primarily in the abdominal cavity, and stromogenic uterine sarcoma. Conclusion . Thus, housing the female rats under the LL and NL conditions led to a significantly faster development of spontaneous tumors compared to the animals under the LD conditions. Light deprivation reduced the tumor incidence rate. Apparently, a lack of melatonin or an abnormality in the rhythm pattern of its secretion is the cause of the accelerated development of neoplasms. An essential modifying factor of carcinogenesis is a disturbance in the normal natural alternation of light and dark periods, resulting in desynchronization of the organism's circadian rhythms. Exposure to light at night can be considered as one of the environmental factors leading to disordering of homeostasis and carcinogenesis. The results of our studies allow us to substantiate the fundamentally important position that desynchronosis of the activity of the epiphysis, caused by light pollution or seasonal fluctuations in illuminance, leads to an increase in the incidence rate of neoplasms. A comprehensive assessment of this sort of impacts is possible with the use of an adequate experimental model. Rats can serve as such model, since melatonin secretion in these animals has the same circadian rhythm as it is the case with humans. The longitudinal research method used in our experiment is the most adequate one, since it involves observing the same animals over a long period from youth to old age and death. This approach makes it possible to correctly compare the studied parameters in different experimental groups.