Effects of 6-month daily supplementation with oral beta-carotene in combination or not with benzo\[a\]pyrene on cell-cycle markers in the lung of ferrets

Our plain-English summary of Effects of 6-month daily supplementation with oral beta-carotene in combination or not with benzo[a]pyrene on cell-cycle markers in the lung of ferrets, by A. Fuster, C. Picó, J. Sánchez, et al (The Journal of Nutritional Biochemistry, 2008).

The study

• Authors: A. Fuster, C. Picó, J. Sánchez, P. Oliver, M.C. Zingaretti, I. Murano, M. Morroni, U. Hoeller, R. Goralczyk, S. Cinti, A. Palou
• Journal: The Journal of Nutritional Biochemistry
• Published: 2008;19(5):295-304
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Epidemiological studies have demonstrated that people who eat more fruits and vegetables (rich in carotenoids) and people who have higher serum beta-carotene (BC) levels have a lower risk of cancer, particularly lung cancer. However, the two main human intervention studies of BC supplementation (the ATBC and the CARET trials) revealed an increased risk of lung cancer among smokers and asbestos workers. Previous studies carried out in the ferret have reported that BC effects are related to dose. Here, we treated ferrets with two concentrations of oral BC (0.8 and 3.2 mg/kg body weight per day) for 6 months, using BC in a formulation also containing dl-alpha-tocopherol and ascorbyl palmitate. The effect of the smoke-derived carcinogenic agent benzo[a]pyrene (BP), with or without low-dose BC, was also analysed. We determined the protein levels and mRNA expression levels of activator protein 1 (c-Jun and c-Fos), c-Myc, cyclin D1, proliferating cellular nuclear antigen and retinoic acid receptor beta. We did not find higher levels of cell proliferation markers in the lung of ferrets treated with BC or signals of squamous metaplasia lesions either. On the other hand, although no evident signals of pulmonary carcinogenesis were observed in animals exposed to BP, BC supplementation in these animals may prevent against excess cell proliferation, since this reestablishes Jun protein and cyclin D1 mRNA levels in the lung of BP-exposed animals. In summary, these results show that the combination of BC with alpha-tocopherol and ascorbyl palmitate does not induce pro-oxidant effects in the lung of ferrets.

In plain English

This ferret experiment did not study asbestos; asbestos workers appear only in background, describing earlier human beta-carotene trials. Female ferrets obtained at seven weeks old were, after one week of adaptation, randomly assigned to five groups of six: controls, low-dose beta-carotene (0.8 mg/kg body weight per day), high-dose beta-carotene (3.2 mg/kg per day), benzo[a]pyrene (a tobacco-smoke carcinogen), and benzo[a]pyrene plus low-dose beta-carotene. Beta-carotene, in a formulation also containing dl-alpha-tocopherol and ascorbyl palmitate, was given by mouth daily for 6 months; benzo[a]pyrene was given by mouth three times weekly for 10 weeks, starting one week after beta-carotene began. The authors measured lung cell-growth markers and examined lung tissue microscopically. No significant lung lesions or squamous metaplasia were found in any group. PCNA, a proliferation marker, was unaffected by either treatment. Benzo[a]pyrene raised Jun protein, but not in animals also given low-dose beta-carotene, and lowered RAR-beta levels. The authors concluded that this beta-carotene formulation did not induce pro-oxidant effects in ferret lungs. They noted that a preventive effect of the vitamins, also given in the placebo, could not be ruled out.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment (randomized treatment groups of ferrets, 6-month treatment)
• Who was studied: Female ferrets obtained at seven weeks old from Exopet AB (Glommen, Sweden). After 1 week of adaptation they were randomized into five groups of six animals. They were kept at the animal house of the University of the Balearic Islands.
• Exposure: Oral beta-carotene at 0.8 or 3.2 mg/kg body weight per day for 6 months, in a formulation with dl-alpha-tocopherol and ascorbyl palmitate. Oral benzo[a]pyrene at 8 mg/kg per dose, three times per week for 10 weeks (total 240 mg/kg), starting 1 week after beta-carotene treatment began, alone or with low-dose beta-carotene. No asbestos exposure was studied.
• Main results:
  • Plasma beta-carotene rose with dose. Levels in the low-dose group were not statistically different from controls; levels in the high-dose group were significantly higher.
  • No significant lung lesion was found in any animal in any group, and no squamous metaplasia was seen in treated ferrets.
  • Lung PCNA protein and mRNA levels were not affected by beta-carotene or benzo[a]pyrene.
  • Ferrets given benzo[a]pyrene alone had higher Jun protein levels than controls. No increase was found in benzo[a]pyrene-treated ferrets also given low-dose beta-carotene.
  • Lung RAR-beta levels were significantly reduced by benzo[a]pyrene treatment, both with and without beta-carotene.
  • Myc protein fell significantly (41%) in the high-dose beta-carotene group compared with controls.
  • Cyclin D1 levels in lung fell (33%) in the low-dose beta-carotene group compared with controls and were unchanged in the high-dose group.
  • At the end of treatment, body weight in the high-dose beta-carotene group was 14% higher than in controls; low-dose beta-carotene made no significant change.
• The authors' conclusion: The authors concluded that beta-carotene combined with alpha-tocopherol and ascorbyl palmitate did not induce pro-oxidant effects in ferret lungs. They suggested that, besides dose, the formulation (presence of antioxidants) may matter for whether beta-carotene protects against or promotes cancer.
• Limitations the authors state:
  • Benzo[a]pyrene produced no clear lung tumour effects. The authors could not rule out a preventive effect of the alpha-tocopherol and ascorbate that were also in the placebo.
  • mRNA and protein levels did not always agree, particularly in animals given benzo[a]pyrene.
  • No earlier ferret studies had used benzo[a]pyrene to induce lung tumours, so the dose was taken from mouse studies.

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Carcinogenic, Carcinogenesis.

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• Beta carotene: from biochemistry to clinical trials — W.A. Pryor, W. Stahl, et al. (2000)
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• The enigma of beta-carotene in carcinogenesis: what can be learned from animal studies — R.M. Russell (2004)

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