Hypothesis: Phenol and hydroquinone derived mainly from diet and gastrointestinal flora activity are causal factors in leukemia

Abstract

High background levels of phenol and hydroquinone are present in the blood and urine of virtually all individuals, but vary widely. Phenol and hydroquinone have been strongly implicated in producing leukemia associated with benzene exposure, because they reproduce the hematotoxicity of benzene, cause DNA and chromosomal damage found in leukemia, inhibit topoisomerase II, and alter hematopoiesis and clonal selection. The widely varying background levels of phenol and hydroquinone in control individuals stem mainly from direct dietary ingestion, catabolism of tyrosine and other substrates by gut bacteria, ingestion of arbutin-containing foods, cigarette smoking, and the use of some over-the-counter medicines. We hypothesize that these background sources of phenol and hydroquinone and associated adducts play a causal role in producing some forms of de novo leukemia in the general population. This hypothesis is consistent with recent epidemiological findings associating leukemia with diets rich in meat and protein, the use of antibiotics (which change gastrointestinal flora make-up), lack of breastfeeding, and low activity of NAD(P)H quinone oxidoreductase which detoxifies quinones derived from phenol and hydroquinone and protects against benzene hematotoxicity. An attractive feature of our hypothesis is that it may explain why many people who have no known occupational exposures or significant smoking history develop leukemia. The hypothesis predicts that susceptibility to the disease would be related to diet, medicinal intake, genetics and gut-flora composition. The latter two of these are largely beyond our control, and thus dietary modification and reduced use of medicines that elevate phenol levels may be the best intervention strategies for lowering leukemia risk. Leukemia (2001) 15, 10-20.

In vitro assessment of the cytotoxic, DNA damaging, and cytogenetic effects of hydroquinone in human peripheral blood lymphocytes

“…We believe these findings are particularly important from the toxicological point of view because of the fact that human exposure to hydroquinone in some cases can be relatively high. Besides occupational exposure, which is limited to specific work settings (e.g., production of hydroquinone, photographic developers, rubber, and other products that contain hydroquinone), there are many sources of Jurica hydroquinone in otherwise "unexposed" people, which include smoking, consumption of different foods and beverages, use of various herbal preparations and over-thecounter medicines (for instance paracetamol or acetaminophen), as well as the catabolism of proteins (especially the amino acid tyrosine) and other substrates by microorganisms in the digestive system (2,8,43). An example of a food item very rich in free hydroquinone is pear, with 0.02-0.05 µg g -1 (8).…”

The role of human biological monitoring in health risk assessment

“…For example, phenol is one of the major metabolites of benzene. However, urinary phenol measurement is not a good indicator of benzene exposure as phenol also occurs naturally and can be found in other exposures such as cigarette smoke (McDonald et al, 2001;Arnold et al, 2013). Non-specificity could also arise from endogenous production of a biomarker in the body (e.g., ethylene oxide).…”

Causality of myelodysplasia and acute myeloid leukemia and their genetic abnormalities

“…Experience from chemotherapy-related MDS and AML may also help in identifying new important chemical exposures, as exemplified by recent studies suggesting that consumption of natural products and medicines, 115 and absorption of phenol and hydroquinone from the gastrointestinal tract, 116 may be responsible for some cases of de novo MDS and AML.…”