Effect of butylated hydroxytoluene on biliineage differentiation of the human HL‐60 myeioblastic leukemia cell

Cp, Burns; Es, Petersen

doi:10.1002/jcp.1041440106

Cited by 4 publications

(1 citation statement)

References 16 publications

(22 reference statements)

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“…Both BHT and BHA accelerated retinoic acid-induced myelocytic differentiation and dihydroxyvitamin D 3 -induced monocytic differentiation in human HL-60 myeloblastic leukemia cells, whereas other antioxidants and eicosanoid synthesis inhibitors did not modify cell differentiation (Burns and Petersen 1990).…”

Section: Miscellaneous Effectsmentioning

confidence: 87%

Final Report on the Safety Assessment of BHT

Lanigan¹,

Yamarik²

2002

Int J Toxicol

141

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BHT is the recognized name in the cosmetics industry for butylated hydroxytoluene. BHT is used in a wide range of cosmetic formulations as an antioxidant at concentrations from 0.0002% to 0.5%. BHT does penetrate the skin, but the relatively low amount absorbed remains primarily in the skin. Oral studies demonstrate that BHT is metabolized. The major metabolites appear as the carboxylic acid of BHT and its glucuronide in urine. At acute doses of 0.5 to 1.0 g/kg, some renal and hepatic damage was seen in male rats. Short-term repeated exposure to comparable doses produced hepatic toxic effects in male and female rats. Subchronic feeding and intraperitoneal studies in rats with BHT at lower doses produced increased liver weight, and decreased activity of several hepatic enzymes. In addition to liver and kidney effects, BHT applied to the skin was associated with toxic effects in lung tissue. BHT was not a reproductive or developmental toxin in animals. BHT has been found to enhance and to inhibit the humoral immune response in animals. BHT itself was not generally considered genotoxic, although it did modify the genotoxicity of other agents. BHT has been associated with hepatocellular and pulmonary adenomas in animals, but was not considered carcinogenic and actually was associated with a decreased incidence of neoplasms. BHT has been shown to have tumor promotion effects, to be anticarcinogenic, and to have no effect on other carcinogenic agents, depending on the target organ, exposure parameters, the carcinogen, and the animal tested. Various mechanism studies suggested that BHT toxicity is related to an electrophillic metabolite. In a predictive clinical test, 100% BHT was a mild irritant and a moderate sensitizer. In provocative skin tests, BHT (in the 1% to 2% concentration range) produced positive reactions in a small number of patients. Clinical testing did not find any depigmentation associated with dermal exposure to BHT, although a few case reports of depigmentation were found. The Cosmetic Ingredient Review Expert Panel recognized that oral exposure to BHT was associated with toxic effects in some studies and was negative in others. BHT applied to the skin, however, appears to remain in the skin or pass through only slowly and does not produce systemic exposures to BHT or its metabolites seen with oral exposures. Although there were only limited studies that evaluated the effect of BHT on the skin, the available studies, along with the case literature, demonstrate no significant irritation, sensitization, or photosensitization. Recognizing the low concentration at which this ingredient is currently used in cosmetic formulations, it was concluded that BHT is safe as used in cosmetic formulations.

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Section: Miscellaneous Effectsmentioning

confidence: 87%

Final Report on the Safety Assessment of BHT

Lanigan¹,

Yamarik²

2002

Int J Toxicol

141

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Enhancement by other compounds of the anti-cancer activity of vitamin D3 and its analogs

Danilenko

Studzinski

2004

Experimental Cell Research

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Butylated hydroxytoluene modulates DNA methylation in rats

Vanyushin¹,

Lopatina²,

Wise³

et al. 1998

European Journal of Biochemistry

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The major observation of this investigation is that a single intraperitoneal injection of butylated hydroxytoluene (BHT, 60 mg/kg body mass) results within a few hours in a strong increase in nuclear DNA(cytosine-5)-methyl transferase (methyl transferase) activity in the liver, kidneys, heart, spleen, brain and lungs of male rats. In most organs, the rise in methyl transferase activity is observed as early as 4 h after BHT injection, it reaches a maximum at 8 h and then, except for lungs and brain, gradually decreases to its initial level at 16 h. At the maximum induction times, the methyl transferase activity in liver, kidney and spleen increases by about 16-, 3-and 5-fold, respectively. A second BHT injection at 96 h results in a secondary rise in hepatic methyl transferase activity. Isoelectric focusing electrophoresis of control rat liver nuclear extracts showed methyl transferase activity in the pI 4.7 and 7.4 protein fractions. Both fractions methylate calf thymus DNA better than they do Drosophila melanogaster DNA. In similar extracts from BHT-treated rats, the methyl transferase activity is found in three protein fractions with pI values equal to 4.0, 6.2 and 9.5, respectively. Most of the methyl transferase fractions from the livers of BHT-treated rats methylate the completely unmethylated D. melanogaster DNA better than they do calf thymus DNA. Thus, BHT induces methyl transferase activity that preferably provides de novo DNA methylation. BHT injection had no significant effect on the hepatic contents of S-adenosylmethionine (AdoMet), S-adenosylhomocysteine (AdoHcy) and AdoMet/AdoHcy ratios. While BHT injection did not alter the 5-methyldeoxycytidine content in liver DNA, it did appear to alter such content in other organs. BHT appears to cause the reversible changes in the methylation status of an internal cytosine residue in some CCGG sites of the rat liver cytosine DNA-methyl transferase gene. BHT induces also hypomethylation of the renal methyl transferase gene and the hepatic c-Ha-ras gene. While BHT also increases the hepatic mRNA transcripts for the S-adenosylmethionine synthetase and the p53 genes, it had no detectable effects on the corresponding mRNA transcripts for methyl transferase homologous to murine methyl transferase. Thus, BHT induces tissue-specific reversible changes in methyl transferase activity and methylation of total DNA and various genes in rats. A strong increase in methyl transferase activity in rat liver is accompanied with BHT-induced change in the methyl transferase set observed in this organ.

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Effect of butylated hydroxytoluene on biliineage differentiation of the human HL‐60 myeioblastic leukemia cell

Cited by 4 publications

References 16 publications

Final Report on the Safety Assessment of BHT

Final Report on the Safety Assessment of BHT

Enhancement by other compounds of the anti-cancer activity of vitamin D3 and its analogs

Butylated hydroxytoluene modulates DNA methylation in rats

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