Effects of β-carotene on chemically-induced skin tumors in HRASkh hairless mice

Steinel, H.H.; Baker, R.S.U.

doi:10.1016/0304-3835(90)90052-y

Cited by 20 publications

(3 citation statements)

References 11 publications

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“…Protective effects of ␤-carotene were observed against colon cancer, 19 -22 with a significant potential to inhibit ACF, the putative preneoplastic lesions in the colon. Similarly, ␤-carotene supplementation significantly reduced cancer of the skin, 23 liver, 24 pancreas, 25 oral cavity 26 and stomach. 27 By contrast, no effect of ␤-carotene supplementation was observed in a rat colon cancer model, 27 nor were promotional effects seen in studies using the mouse skin cancer model, 28 the ferret lung cancer model 29 or the mouse Ehrlich ascites model.…”

mentioning

confidence: 91%

Low doses of β‐carotene and lutein inhibit AOM‐induced rat colonic ACF formation but high doses augment ACF incidence

Raju

Swamy

Cooma

et al. 2004

Intl Journal of Cancer

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Epidemiological studies suggest that carotenoids such as ␤-carotene and lutein play an important role in reducing the risk for several cancers. However, in colon cancer there is ambiguity with regard to the role of these compounds in that both preventive effects and tumor promotion have been observed. In the present study we observed that male F344 rats were able to tolerate up to 2,500 ppm of ␤-carotene as well as of lutein. We have then assessed the chemopreventive efficacy of ␤-carotene and lutein at dose levels of ϳ4 and 8% of the 2,500 ppm tolerated dose (TD) and also ϳ40 and 80% of the TD on azoxymethane (AOM)-induced colon carcinogenesis, using aberrant crypt foci (ACF) as a surrogate biomarker for colon cancer. Throughout the experiments, 5-weekold male F344 rats were fed the control diet (modified AIN-76A) or experimental diets containing 100 or 200 ppm (ϳ4 or 8% of the 2,500 ppm TD), or 1,000 or 2,000 ppm (ϳ40 or 80% of the 2,500 ppm TD) of ␤-carotene and lutein (n‫01؍‬ rats/group). After 2 weeks on the experimental or control diets, all animals were injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). At 14 weeks of age, all rats were killed, and their colons were evaluated for ACF. Administration of 100 or 200 ppm of ␤-carotene inhibited AOM-induced total colonic ACF formation by 24% (p<0.01) and 36% (p<0.001), respectively, whereas lutein at 200 ppm produced a 27% inhibition (p<0.01) yet had no significant effect at the 100 ppm dose level. Surprisingly, administration of 1,000 or 2,000 ppm of ␤-carotene and lutein increased colonic ACF formation in a dose-dependent manner, i.e., to 124% and 144% for the former and 110% and 159% for the latter. These results clearly suggest that further studies are warranted to determine whether the increase in ACF incidence by high doses of ␤-carotene and lutein will also lead to an increase in tumor outcome. Taken together these data indicate that the chemopreventive activity of ␤-carotene and lutein against colon carcinogenesis depends on the dose level. © 2004 Wiley-Liss, Inc. Key words: colon cancer; aberrant crypt foci; chemoprevention; ␤-carotene; lutein Colorectal cancer is one of the leading causes of cancer deaths in both men and women in Western countries, including the United States. 1 Evidence from epidemiological studies and laboratory animal assays suggests a relationship between colon cancer risk and several dietary factors. 2,3 Identification of naturally occurring carcinogens and anti-carcinogens should lead not only to an understanding of carcinogenesis but should also provide strategies for cancer prevention. Several epidemiological studies have consistently demonstrated that people who have a high intake of vegetables and fruits that are rich in carotenoids had low risk of cancer. 4 -7 Possible cancer preventive effects of carotenoids have been established in several epidemiological and clinical studies by comparing serum levels of carotenoids in normal and cancer patients. 8 -10 Some studies also pointed to a possible relationshi...

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confidence: 91%

Low doses of β‐carotene and lutein inhibit AOM‐induced rat colonic ACF formation but high doses augment ACF incidence

Raju

Swamy

Cooma

et al. 2004

Intl Journal of Cancer

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“…In association with β-carotene supplementation, cancer preventive effects have been reported for the following tumours in the animals indicated (IARC, 1998;Moreno et al, 1991;1995;Temple and Basu, 1987;Shivapurkar et al, 1995;Yamamoto et al, 1994;Alabaster et al, 1995;Appel and Woutersen, 1996;Appel et al, 1991;Azuine et al, 1992;Mathews-Roth et al, 1991;Alam and Alam, 1987) in skin (mice), liver (rats), colon (rats, mice), pancreas (rats, hamsters), forestomach (mice), bladder (mice), salivary gland (rats) and adenocarcinomas and nephroblastomas (rats). Other studies (Mathews-Roth and Krinsky, 1987;Steinel et al, 1990;Astorg et al, 1996Astorg et al, , 1997Colacchio and Memoli, 1986;Jones et al, 1989;Appel et al, 1996;Pedrick et al, 1990;Colacchio et al, 1989;Alam et al, 1984Alam et al, , 1988 have shown no effect of β-carotene supplementation on the incidence of tumours of the skin (mice), liver (mice, rats), colon (rats), pancreas (rats, hamsters), glandular stomach (rats), bladder (mice, rats), small intestine (rats), and salivary gland (rats).…”

Section: Chronic Toxicity and Carcinogenicity β-Carotene [E 160a (Ii)]mentioning

confidence: 97%

Scientific Opinion on the re‐evaluation of mixed carotenes (E 160a (i)) and beta‐carotene (E 160a (ii)) as a food additive

2012

EFS2

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The Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion reevaluating the safety of mixed carotenes [E 160a (i)] and β-carotene [E 160a (ii)] when used as food colouring substances. Mixed carotenes [E 160a (i)] and β-carotene [E 160a (ii)] are authorised as food additives in the EU and have been evaluated previously by the JECFA the latest in 2001 and by the SCF in 1997 and 2000. Both Committees established an Acceptable Daily Intake (ADI) of 0-5 mg/kg bw/day. In this opinion the mixed carotenes are defined according to the Commission Directive 2008/128/EC and consist of two groups of substances: plant carotenes and algal carotenes. β-Carotene comprises (synthetic) β-carotene and β-carotene obtained by fermentation of the fungus Blakeslea trispora. The Panel noted (i) that the specifications of mixed carotenes are inadequate and need to be updated, (ii) that most toxicological studies have been performed with rodents, although rodents, in contrast to humans, very efficiently convert β-carotene to vitamin A. The Panel concluded that based on the presently available dataset, no ADIs for mixed carotenes and β-carotene can be established and that the use of (synthetic) β-carotene and mixed β-carotenes obtained from palm fruit oil, carrots and algae as food colour is not of safety concern, provided the intake from this use as a food additive and as food supplement, is not more than the amount likely to be ingested from the regular consumption of the foods in which they occur naturally (5-10 mg/day). This would ascertain that the exposure to βcarotene from these uses would remain below 15 mg/day, the level of supplemental intake of βcarotene for which epidemiological studies did not reveal any increased cancer risk. Furthermore, the Panel could not conclude on the safety in use of mixed carotenes [E 160a (i)] for the preparatory work on this scientific opinion.Re-evaluation of mixed carotenes (E 160a (i)) and β-carotene (E 160a (ii)) as food additives EFSA Journal 2012;10(3):2593 2 SUMMARY Following a request from the European Commission to the European Food Safety Authority (EFSA), the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to deliver a scientific opinion re-evaluating the safety of mixed carotenes [E 160a (i)] and β-carotene [E 160a (ii)] when used as food colour. Mixed carotenes [E 160a (i)] and β-carotene [E 160a (ii)] are authorised as food additives in the European Union (EU) and have been evaluated previously by the Joint FAO/WHO/Expert Committee on Food Additives (JECFA) in 1975 (β-carotene), 1993 (carotenes from natural sources) and 2001 (βcarotene derived from Blakeslea trispora), and by the EU Scientific Committee for Food (SCF) in the EU in 1975, 1997 (β-carotene derived from Dunaliella salina) and 2000 (β-carotene derived from Blakeslea trispora). The SCF and JECFA both established an Acceptable Daily Intake (ADI) of 0-5 mg/kg bw/day.JECFA defined the ADI for the sum of the carotenoids β-apo-8'-carotenal, β-carotene, β-carot...

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“…Prior to 1995, substantial epidemiologic evidence was seen as supportive of the hypothesis that b-carotene was the primary bioactive component in fruit that reduced cancer risk (Wald, 1987;Willett, 1990;Lippman et al, 1993;Hennekens, 1994), and specifically reduced lung-cancer risk (Willett, 1990). Moreover, limited studies from animals (Schwartz and Shklar, 1988;Lambert et al, 1990;Steinel and Baker, 1990;Appel et al, 1991;Moreno et al, 1991;Sherenesheva and Fin'ko, 1992;Chen et al, 1993) and cultured cell models (Hazuka et al, 1990;Nyandieka et al, 1990;Schwartz et al, 1990;Bertram et al, 1991;Zhang et al, 1991;Das et al, 1992;Moon et al, 1992;Cooney et al, 1993) supported this hypothesis (although very few studies were conducted in models of lung cancer) (Castonguay et al, 1991). A mechanistic hypothesis was developed that explained b-carotene's function as an in vivo antioxidant that protected against oxidation-induced cellular damage (Di Mascio et al, 1990;Dorgan and Schatzkin, 1991;Malone, 1991;Borek, 1993).…”

Section: B-carotenementioning

confidence: 99%

Proposed Criteria for Assessing the Efficacy of Cancer Reduction by Plant Foods Enriched in Carotenoids, Glucosinolates, Polyphenols and Selenocompounds

Finley

2005

Annals of Botany

153

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The evidence of efficacy is weak for carotenoids and polyphenols; the evidence is stronger for glucosinolates and lycopene, but production of enriched foods still is premature. Additionally there is unacceptable variability in the amount and chemical form of these compounds in plants. The evidence of efficacy for selenocompounds is strong, but the clinical study that is potentially the most convincing is still in progress; also the variability in amount and chemical form of Se in plants is a problem. These gaps in understanding bioactive compounds and their health benefits should not serve to reduce research interest but should, instead, encourage plant and nutritional scientists to work together to develop strategies for improvement of health through food.

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Effects of β-carotene on chemically-induced skin tumors in HRASkh hairless mice

Cited by 20 publications

References 11 publications

Low doses of β‐carotene and lutein inhibit AOM‐induced rat colonic ACF formation but high doses augment ACF incidence

Low doses of β‐carotene and lutein inhibit AOM‐induced rat colonic ACF formation but high doses augment ACF incidence

Scientific Opinion on the re‐evaluation of mixed carotenes (E 160a (i)) and beta‐carotene (E 160a (ii)) as a food additive

Proposed Criteria for Assessing the Efficacy of Cancer Reduction by Plant Foods Enriched in Carotenoids, Glucosinolates, Polyphenols and Selenocompounds

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