Modulation of Tumor Development by Butylated Hydroxytoluene in Experimental Animals

Witschi, Hanspeter

doi:10.1177/0748233793009001-219

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…Depending on the organ, animal strain and administered carcinogen, BHT may show a tumour prophylactic effect, no effect on the tumour incidence, or tumourpromoting effect as reviewed (Malkinson, 1983;IARC, 1986;Witschi, 1993). Although exceptions exist, BHT administered prior to or concomitantly with the carcinogen treatment decreased the tumour incidence, whereas BHT often acted as a promotor if administered after the carcinogen exposure had occurred (Lindenschmidt et al, 1986;Matzinger et al, 1994;Wang and Witschi, 1995;and the reviews Malkinson, 1983;IARC, 1986;German Chemical Society, 1994;Witschi, 1993).…”

Section: Carcinogenic Effectmentioning

confidence: 99%

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Indoor Air Guideline Levels for Phenol and Butylated Hydroxytoluene (BHT)

Nielsen¹,

Hansen²,

Nexø³

et al. 1998

Indoor Air

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Sensory and health effects of phenol and butylated hydroxytoluene (BHT) are evaluated based on published literature, and guideline values for exposure limits in indoor air are proposed. The sensory effects are evaluated from odour thresholds and exposure limits preventing sensory irritation, i.e. irritation of eyes and nose. Health effects are evaluated from two types of effect: firstly lung effects and non‐carcinogenic systemic effects; and secondly genotoxic and carcinogenic effects. Both types of effect were evaluated with a view to setting guideline values.

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Section: Carcinogenic Effectmentioning

confidence: 99%

“…Therefore, cell proliferation was not believed to explain the liver effects (Clayson et al, 1993). Finally, it should be recognized that the BHT doses required to modulate tumour development are quite high and it is uncertain whether the much lower exposures to humans produce any biological effects at all (Witschi, 1993).…”

Section: Carcinogenic Effectmentioning

confidence: 99%

Indoor Air Guideline Levels for Phenol and Butylated Hydroxytoluene (BHT)

Nielsen¹,

Hansen²,

Nexø³

et al. 1998

Indoor Air

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show abstract

Oxygen radical detoxification processes during aging:The functional importance of melatonin

Reíter

1995

Aging Clin Exp Res

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Strain-dependent lung tumor formation in mice transplacentally exposed to 3-methylcholanthrene and post-natally exposed to butylated hydroxytoluene

et al. 1999

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The carcinogenic effects of in utero exposure to 3-methylcholanthrene (MC) have been demonstrated in the tumor-resistant C57BL/6 (B6) and DBA (D2) strains of mice. In this study, we determined the effects of in utero exposure to MC in BALB/c mice, a strain which demonstrates greater susceptibility to lung tumor induction, and compared our findings with those previously found in [D2xB6D2F(1)]F(2) mice. In addition, we assessed the molecular pathogenesis of the chemically induced tumors and examined the effects of the putative lung tumor promoter butylated hydroxytoluene (BHT) in BALB/c mice. BALB/c mice were treated on day 17 of gestation with 5, 15 or 45 mg/kg MC and 6 weeks after birth with BHT for 6 consecutive weeks. Mice were killed at 6 months of age. Ki-ras, p16Ink4a and p19ARF gene loci were amplified from paraffin-embedded lung tumor tissue and screened for the presence of point mutations via allele-specific oligonucleotide hybridization and single strand conformation polymorphism (SSCP) analyses. Ki-ras point mutations were found in 56% (20/36) of BALB/c lung tumors, with 33% (2/6) of the hyperplasias, 58% (10/19) of the adenomas and 73% (8/11) of the carcinomas exhibiting point mutations at this gene locus. Similar incidences of Ki-ras mutations were previously found following transplacental exposure of [D2xB6D2F(1)]F(2) mice to MC and treatment of adult A/J mice with urethane. Interestingly, a strain-dependent difference was observed in the mutational spectrum. Sixty-two and 38% of the lung lesions in BALB/c mice exhibited G-->C and G-->T transversions, respectively, in contrast to the 13 and 84% incidences previously observed in [D2xB6D2F(1)]F(2) mice. SSCP analysis of the tumor suppressor gene p16Ink4a showed a 6% incidence of point mutations, consistent with that found in [D2xB6D2F(1)]F(2) mice. No mutations were found in exon 1beta of the p19ARF gene of either strain. BHT, a lung tumor promoter in adult mice, had no statistically significant effects on either tumor incidence, tumor multiplicity or the mutational spectrum produced in the Ki-ras gene by in utero MC treatment. However, though not significant, there was an observable trend in increased tumor multiplicity in mice co-treated with BHT. These data demonstrate the transplacental carcinogenic effect of MC in BALB/c mice and show that mutagenic damage to Ki-ras is a critical early event mediating murine lung tumorigenesis in both the tumor-sensitive and tumor-resistant strains. Unlike what occurs when adult BALB/c mice are treated with MC, BHT does not appear to significantly promote the formation of lung tumors following transplacental exposure to MC, possibly due to the rapid growth and cell proliferation in the developing organism. Strain-dependent differences in the Ki-ras mutational spectrum may be associated with their differential susceptibility to lung tumor initiation.

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Modulation of Tumor Development by Butylated Hydroxytoluene in Experimental Animals

Cited by 4 publications

References 38 publications

Indoor Air Guideline Levels for Phenol and Butylated Hydroxytoluene (BHT)

Indoor Air Guideline Levels for Phenol and Butylated Hydroxytoluene (BHT)

Oxygen radical detoxification processes during aging:The functional importance of melatonin

Strain-dependent lung tumor formation in mice transplacentally exposed to 3-methylcholanthrene and post-natally exposed to butylated hydroxytoluene

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