Singletary K W
Division of Foods and Nutrition, School of Human Resources and Family Studies, University of Illinois, Urbana 61801.
Cancer Lett. 1990 Mar;49(3):187-93. doi: 10.1016/0304-3835(90)90157-s.
The effect of dietary intake of butylated hydroxytoluene (BHT) (0.6%) on the in vivo distribution, metabolism and DNA-binding of intragastrically administered 7,12-dimethylbenz[a]anthracene (DMBA) was evaluated. Urinary excretion of DMBA increased, blood content of metabolized DMBA increased and blood content of non-metabolized DMBA decreased for rats fed the diet containing BHT as compared to rats fed the control diet. The binding of DMBA to both liver and mammary DNA decreased for rats fed the diet containing BHT as compared to controls. The liver activities of glutathione-S-transferase (GST), epoxide hydrolase (EH) and NAD(P)H-quinone reductase (QR) increased in response to BHT feeding. However, no increase in the mammary tissue activities of these enzymes was observed. These results suggest that the ability of dietary BHT to inhibit the initiation of DMBA-induced mammary carcinogenesis partly may be due to decreased binding of DMBA to mammary DNA. This effect of BHT is not due to an increase in mammary tissue activities of GST, EH and QR, enzymes involved in carcinogen detoxification, but may involve increased liver metabolism of DMBA to products that do not bind to DNA.
评估了膳食中摄入丁基羟基甲苯（BHT，0.6%）对经胃内给予7,12-二甲基苯并[a]蒽（DMBA）的体内分布、代谢及与DNA结合的影响。与喂食对照饮食的大鼠相比，喂食含BHT饮食的大鼠，DMBA的尿排泄增加，代谢后的DMBA血液含量增加，未代谢的DMBA血液含量降低。与对照相比，喂食含BHT饮食的大鼠，DMBA与肝脏和乳腺DNA的结合均减少。喂食BHT后，肝脏中谷胱甘肽-S-转移酶（GST）、环氧化物水解酶（EH）和NAD(P)H-醌还原酶（QR）的活性增加。然而，未观察到这些酶在乳腺组织中的活性增加。这些结果表明，膳食BHT抑制DMBA诱导的乳腺癌发生起始的能力，部分可能是由于DMBA与乳腺DNA的结合减少。BHT的这种作用并非由于参与致癌物解毒的GST、EH和QR在乳腺组织中的活性增加，而是可能涉及DMBA在肝脏中代谢为不与DNA结合的产物增加。
