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Se-enriched vegetables and cancer reduction. P. D. WHANGER, PhD. Department of Environmental & Molecular Toxicology Oregon State University Corvallis, OR. 97330. Low. Variable. Adequate. Accumulators. SELENIUM LEVELS. Epidemiological Studies. Shamberger and Frost - PowerPoint PPT Presentation
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Se-enriched vegetables and cancer reductionSe-enriched vegetables and cancer reduction
P. D. WHANGER, PhD.P. D. WHANGER, PhD.Department of Environmental & Department of Environmental &
Molecular ToxicologyMolecular Toxicology
Oregon State UniversityOregon State UniversityCorvallis, OR. 97330Corvallis, OR. 97330
Low
Variable
Adequate
Accumulators
SELENIUM LEVELS
Shamberger and Frost Can. Med. Assoc. J. 104:82 (1969)—reported inverse relationship of selenium intake with cancer
Shamberger and WillisCRC Crit. Rev. Clin. Lab. Sci. 2: 211 (1971)—more detailed study showing this same inverse relationship
Schrauzer et alBioinorganic Chem. 7:23 (1977)--27-country comparison revealed certain cancers varied inversely with estimated per capita selenium intake
Epidemiological StudiesEpidemiological Studies
Selenium and Tumors with Small AnimalsSelenium and Tumors with Small Animals
There have been over 100 experiments conducted (Combs and Gray, Pharmacol. Ther. 79: 179 (1998)
(a)Two-thirds of animal studies showedstatistically significant reductions of tumors by selenium
(b)One-half showed reductions of 50% or more by selenium
Modified From J. Amer. Med. Assoc. 276: 1957 (1996)Modified From J. Amer. Med. Assoc. 276: 1957 (1996)
Effects of Selenium on Cancer in HumansEffects of Selenium on Cancer in Humans
H2Se
Proteins
Selenocysteine
SeO4
GSSeH
GSSeSG
SeO3
ATP
Se-adenosylselenomethionine
Selenomethionine
Selenohomocysteine
Selenocystathionine
Succinyl homocysteine
Acetate
Acetylserine
-keto--methyl selenobutyrate
Se-methylselenocysteine
glutamine
dimethylselenopropionate
GSH
ATP
adenosine
Se-adenosylselenocysteine
Se-methylselenomethionine
-glutamyl –Se methyl Selenocysteine
-glutamyl Selenocystathionine
GSSG
ADP
ADP
Succinate
Se-methylSeCysSe-oxide
Dimethyldiselenide
dimethyl selenide
(CH3)3Se+
(CH3)2Se
CH3SeH
H2Se
GS-Se-SG
GS-SeH
SeO3
SeO4
selenophosphate
Selenoproteins(as selenocysteine)
selenocysteine
selenomethionine
General body proteins
-glutamyl-Se-methyl selenocysteine
Se-methyl selenocysteine
methyl seleno propionate
-keto--methyl selenobutyrate
selenocystathionine
Anticarcinogenic Efficacy of Different Selenium CompoundsAnticarcinogenic Efficacy of Different Selenium Compounds for Reduction of Mammary Tumors in Ratsfor Reduction of Mammary Tumors in Rats
Nutr. Cancer 17:279 (1992)Nutr. Cancer 17:279 (1992)
Mammary Tumors in Rats Fed Various DietsMammary Tumors in Rats Fed Various Diets
Effect of Selenium on the Incidence of Tumors in RatsEffect of Selenium on the Incidence of Tumors in Rats Injected with MethylnitrosoureaInjected with Methylnitrosourea
Mammary Cancer Prevention in Rats Fed Different Mammary Cancer Prevention in Rats Fed Different Sources of SeleniumSources of Selenium
Effect of Dietary Form of Selenium on Tissue Selenium Effect of Dietary Form of Selenium on Tissue Selenium Concentrations in RatsConcentrations in Rats
JJ. Agric Food Chem. 49: 2681 (2001). Agric Food Chem. 49: 2681 (2001)
CarcinogenesisCarcinogenesis 15: 573 (1994) 15: 573 (1994)
Tissue Selenium Levels in Rats Fed Different Tissue Selenium Levels in Rats Fed Different Sources of SeleniumSources of Selenium
Mammary cancer prevention by selenium enriched garlic orMammary cancer prevention by selenium enriched garlic orselenium enriched yeast in the DMBA and MNU modelsselenium enriched yeast in the DMBA and MNU models
Percent Composition of Identified Selenium Species Percent Composition of Identified Selenium Species of Selenized Garlic and Yeastof Selenized Garlic and Yeast
J. Agric Chemistry, 48:2065 (2000)J. Agric Chemistry, 48:2065 (2000)
J. Agric. Food Chem., Vol: 48, No. 6, 2000
Figure 6. Structures of -glutamyl-Se-methylselenocysteine, Se-methylselenocysteine, and selenomethionine.
NH-CO-CH2-CH2-CH(NH2)-COOH |CH3-Se-CH2-CH-COOH
(-glutamyl-Se-methylselenocysteine)
CH3-Se-CH2-CH(NH2)-COOH
(Se-methylselenocysteine)
CH3-Se-CH2-CH2-CH(NH2)-COOH
(Selenomethionine)
Percentages of Total Selenium as SeMCYS Percentages of Total Selenium as SeMCYS in Selenium Enriched Plantsin Selenium Enriched Plants
Summarized in J. American College of Nutrition 21: 223 (2002)Summarized in J. American College of Nutrition 21: 223 (2002)
Ramps
Garlic
Onions
Broccoli florets
Broccoli sprouts
35-60
47-87
42-55
63
45
Plants% Se as SeMCYS
Effect of Dietary Form of Selenium on Total Number Effect of Dietary Form of Selenium on Total Number of Aberrant Crypt Foci in Ratsof Aberrant Crypt Foci in Rats
JJ. Agric Food Chem. 49: 2681 (2001). Agric Food Chem. 49: 2681 (2001)
Effect of Dietary Form and Amount of Selenium on Colon Tumors in RatsEffect of Dietary Form and Amount of Selenium on Colon Tumors in Rats
JJ. Nutr. 130:2384 (2000). Nutr. 130:2384 (2000)
Wheat and Broccoli
• High Selenium wheat reduced colon tumors in rats but selenomethionine was not very effective in this reduction. Biofactors 14: 191 (2001).
• High selenium broccoli reduced colon tumors in rats, but will SEMCYS be effective (Finley, personal communication)
• SELENOMETHIONINESELENOMETHIONINE- Primary form of Se in enriched yeast, wheat, corn, rice and
soybeans
• Se-METHYLSELENOCYSTEINESe-METHYLSELENOCYSTEINE- Primary form of Se in Astragalus, enriched garlic, broccoli (florets and sprouts), onions and ramps
300
400
200
100
0
Addition to soil Sprayed on Leaves
Se
in b
rocc
oli
µg
/gm
Uptake of Selenium from Soil versus LeavesUptake of Selenium from Soil versus Leaves
Effects of Sticker on the Uptake of Selenium by BroccoliEffects of Sticker on the Uptake of Selenium by Broccoli
Selenium Uptake by Broccoli Sprouts
0
100
200
300
0 10 20 30
Se concentration in water (µg/ml)
Se
co
nc
. in
Sp
rou
ts (
µg
/g)
ConclusionsConclusions
1. Selenium enriched garlic, broccoli florets, onions and ramps significantly reduced mammary tumors in rats.
2. Selenium enriched broccoli (florets and sprouts) and wheat reduced colon tumors in rats.
3. These selenium enriched vegetables did not result in excessive tissue accumulation of selenium and thus are safe for human consumption.
4. SeMCYS is the most effective selenocompound in plants for reduction of mammary tumors in rats. Methylselenol appears to be the specific selenocompound that is effective against mammary tumors.
Accumulation of Selenium inblood, kidney, and liver fromrats fed a selenium-enriched diet
Accumulation of Selenium inmuscle and testes from ratsfed a selenium-enriched diet
Control SEL SeM SeR SeR+SeM
Control = basal diet SEL = selenate SeM = selenomethionine SeR = Se-enriched ramps
Schematic flow chart showing the main sites where selenobetaine,Se-methyselenocysteine, selenobetaine methyl ester, and dimethyl-selenoxide enter the selenium metabolic pathway.
Selenium in Biology and Human Health, p 173, Springer Verlag, New YorkSelenium in Biology and Human Health, p 173, Springer Verlag, New York
Wheat and Broccoli
• High selenium wheat reduced colon tumors
Acknowledgment
My collegues: C. Ip (Roswell Park Cancer Institute, Buffalo, NY; C. Polan and G. Welbaum, Virginia
Technical University; and P. Uden, University of Massachusetts.
Acknowledgment
• We are grateful to Judy Butler and Yu Sun for doing the selenium analyses and the bioavailability study
• Thanks to R. Hafez and M. Kotrebai for the selenium speciation.
• Thanks to Wendy Werks, John Chandler; Johnny, Ruby, Harvey and Debbie Whanger; Jeannie, Keith, Zemry and Margaret Lou Crookshanks; Wayne and Beverly Hinkle; and Bill Definbaugh who worked on various aspects of this project.