With global industrialization over the last two decades around the world that involves an increase in production, manufacturing, and energy consumption, benzene exposure affects many. With benzene being widely exposed to employee and the public due to its prevalence in industrial discharges, cigarette smoke, vehicle emissions, new buildings, paints, furnitures, sunscreens and even household cleaning products, it is being categorised as a severe environmental pollutant and is officially designated to be a human carcinogen by the International Agency for Research as it strongly affects various tissues and vital physiological processes such as hormone release and blood cells which can lead to lymphoma and acute leukemia. 

Leukemia occurs when blood stem cells (called blasts) multiply uncontrollably, filling up the bone marrow, and preventing the normal maturation of other blood cells that are important for survival, namely red blood cells, platelets and white blood cells. This leads to infections, anaemia and abnormal bleeding. The immature blasts then spill out of the bone marrow into the bloodstream, the lymph nodes, spleen and brain. Leukemia affects the elderly but is also the most common form of cancer in children age 15 and below.

Benzene is broken down primarily in the liver, lungs and bone marrow. The initial step of breakdown leads to the formation of hydroquinone in the lungs and liver. Then, the hydroquinone is converted to benzoquinone in the bone marrow. This latter process is assisted by myeloperoxidase produced by blood steme cells. Benzoquinone is a powerful clastogenic compound that has the ability to produce chromosomal aberrations, chromatid exchange, DNA damages and the inhibition of topoisomerase II. These changes on the genome are the culprit for the onset of uncontrolled multiplication of immature blast cells.

In this blog, we are going to discuss how benzene exposure leads to the onset of leukemia in rats and the protective potential of live microbes in milk kefir might contribute to its protective effects against cancer pathogenesis by controlling inflammation (Ben Dhia et al., 2021).

Rat growth and development

Benzene-treated rats has reduced body weight gain, surface area, food consumption, energy intake and feed efficiency. 

Whole blood cell count

Benzene-treated rats showed a significant reduction in matured functioning WBC, RBC, platelets, hemoglobin and the size of RBCs. Peripheral lymphocyte, monocyte, and granulocyte cells decreased significantly in benzene treated rats.

Pro-inflammatory cytokine expression

Benzene-treated rats displayed a mRNA up-regulation of pro-inflammatory cytokines (IL-6 and IL-1β).

Bone marrow histo-architecture

Benzene-treated rats showed a sharp increase in the percentage of immature blast stem cells. There are also lower amounts of matured blood cells that were grouped and formed many clumps. The altered medullary tissue in bone marrow also showed an elevated bone marrow adiposity (BMA) which is defined as an increase in the proportion of the bone marrow cavity volume occupied by adipocytes (fat cells). This signifies compromised bone quality that is associated with increased age. There were also signs of inflammation with intercellular edema.

Lactic Acid Bacteria (LAB) colony forming unit

Bacterial colonies were lower in feces, colon, and cecum in benzene-treated rats when compared to control.

While milk kefir treatment after benzene exposure did not show significant improvements in the growth and feeding efficiency of the rats, or bring the levels of functional lymphocyte, monocyte, and granulocyte count back to control levels (not exposed to benzene and no kefir treatment), rats with kefir treatment after benzene exposure showed a rich bone marrow with appearance similar to control via histological sections. Treatment with milk kefir also seemed to correct the myelotoxic effect of benzene since the number of adipocytes cells is near to that of control cells. Hematopoietic cells have a normal aspect; cellular and fatty bone marrow distribution seems to be similar to control rats. The number of blasts decreased significantly in the bone marrow of benzene plus kefir–treated rats. This is a promising finding in the protective effect of milk kefir against leukaemia induced by benzene. Milk kefir also has ameliorative effects in the expression levels of pro-inflammatory cytokines (IL-6 and IL-1β). Live LAB count in kefir treated rats after benzene exposure also showed an increment in level as compared to no kefir treatment.

Besides leukemia, the antitumour activity of milk kefir has been reported against many types of cancer (Shiomi et al. 1982). Furuwaka et al. (2000) demonstrated that the polysaccharide fraction isolated from kefir grain reduces proliferation and inhibits pulmonary metastasis in Lewis lung carcinoma in mice. Kefir showed apoptotic and antiproliferative effects on leukemic lymphocytes (Rizk et al. 2009). Chen et al. (2007) demonstrated that kefir extract did not affect normal human mammary cells, but suppressed malignant cell growth. These specific effects suggest that kefir has protective properties that are specific to transformed cells because of the presence of bioactive molecules that exert antitumoral effect against cancer cells.

Reference:

Ben Dhia, O., Lasram, M. M., Harizi, N., Doghri, R., Charfi, L., Souai, N., Najjari, A., Ouzari, H.-I., & Ben-Hadj-Khalifa, S. (2021). Kefir milk alleviates benzene-induced immunotoxicity and hematotoxicity in rats. Environmental Science and Pollution Research, 28(31), 42230–42242. https://doi.org/10.1007/s11356-021-13569-3