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 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.
T A
TA
McDonald
N T
NT
Holland
C
C
Skibola
P
P
Duramad
M T
MT
Smith
D004032:Diet / Q000009:adverse effects; D004064:Digestive System / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000378:metabolism / Q000633:toxicity*; D007938:Leukemia / Q000209:etiology* / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D010636:Phenols / Q000378:metabolism / Q000633:toxicity*
D006873:Hydroquinones; D009153:Mutagens; D010636:Phenols; C031927:hydroquinone