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

High background levels of phenol and hydroquinone are present in the blood and urine of virtually all individuals, but vary widely. Phenol and hydroqu inone have been strongly implicated in producing leukemia associated with b enzene exposure, because they reproduce the hematotoxicity of benzene, caus e DNA and chromosomal damage found in leukemia, inhibit topoisomerase II, a nd alter hematopoiesis and clonal selection. The widely varying background levels of phenol and hydroquinone in control individuals stem mainly from d irect dietary ingestion, catabolism of tyrosine and other substrates by gut bacteria, ingestion of arbutin-containing foods, cigarette smoking, and th e use of some over-the-counter medicines. We hypothesize that these backgro und 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 associ ating leukemia with diets rich in meat and protein, the use of antibiotics (which change gastrointestinal flora make-up), lack of breastfeeding, and l ow activity of NAD(P)H quinone oxidoreductase which detoxifies quinones der ived from phenol and hydroquinone and protects against benzene hematotoxici ty, An attractive feature of our hypothesis is that it may explain why many people who have no known occupational exposures or significant smoking his tory develop leukemia. The hypothesis predicts that susceptibility to the d isease would be related to diet, medicinal intake, genetics and gut-flora c omposition. The latter two of these are largely beyond our control, and thu s dietary modification and reduced use of medicines that elevate phenol lev els may be the best intervention strategies for lowering leukemia risk.