Effect of light chain V region duplication on IgG oligomerization and in vivo efficacy.

A human immunoglobulin G1 (IgG1) antibody oligomer was isolated from a transfected myeloma cell line that produced a monoclonal antibody to group B streptococci. Compared to the IgG1 monomer, the oligomer was significantly more effective at protecting neonatal rats from infection in vivo. The oligomer was also shown to cross the placenta and to be stable in neonatal rats. Immunochemical analysis and complementary DNA sequencing showed that the transfected cell line produced two distinct kappa light chains: a normal light chain (Ln) with a molecular mass of 25 kilodaltons and a 37-kilodalton species (L37), the domain composition of which was variable-variable-constant (V-V-C). Cotransfection of vectors encoding the heavy chain and L37 resulted in production of oligomeric IgG.

Iron retention in iron-fortified rice and use of iron-fortified rice to treat women with iron deficiency: A pilot study.

OBJECTIVES: 1. Evaluate the effect of washing and cooking iron-fortified rice on iron retention and bioavailability. 2. Evaluate the effect of iron-fortified rice on women with iron deficiency anemia. METHODS: 1. Iron-fortified rice (18 mg/100 g as FeSO4) was cooked in Baton Rouge, Louisiana (C), rinsed and cooked (RC), fried and cooked (FC), cooked with extra water (CW), or soaked and cooked with extra water (SCW), and iron retention was determined. 2. Rice samples were cooked in Kampala, Uganda in a lab (C-Uganda) and households using traditional cooking method (TC-Uganda) and iron retention were determined. 3. Seventeen women with iron deficiency (low iron and/or low ferritin) anemia were randomized to 100 g/d of rice (two cooked 0.75 cup servings) for two weeks containing 18 mg/d iron (supplemented) or 0.5 mg/d iron (un-supplemented). Hemoglobin and hematocrit were evaluated at baseline and 2 weeks with other measures of iron metabolism. RESULTS: 1. Iron retention, from highest to lowest, was (C), (RC), (FC), (C-Uganda), (CW), (SCW) and (TC-Uganda). 2. Seventeen women were randomized and 15 completed the study (hemoglobin 10.6 ± 1.6 g, hematocrit 33.7 ± 4.1%), 9 in the iron-fortified rice group and 6 in the un-fortified rice group. The iron-fortified group had a greater increase in hemoglobin (0.82 g, p = 0.0035) and Hematocrit (1.83%, p = 0.0248) with directional differences in other measures of iron metabolism favoring the iron-fortified group. CONCLUSIONS: Iron-fortified rice increased hemoglobin and hematocrit in women with iron-deficient anemia. Iron deficiency and anemia are widespread in Southeast Asia and Africa and undermine development in these regions.

Characterization of biosynthetic IgG oligomers resulting from light chain variable domain duplication.

We have characterized a human IgG1 monoclonal antibody composed of altered light chains. Each light chain consists of two identical variable domains and a kappa constant domain, in association with a normal gamma chain. This antibody assembled biosynthetically into a mixture of stable oligomers and monomers. Employing gel filtration, PAGE, and electron microscopy, we examined the antibody and the nature of the associations involved in oligomer formation. By engineering a protease factor Xa site between the duplicated light chain variable domains and examining the fragments produced following factor Xa cleavage, we demonstrated the association of the IgG monomers occurred through their duplicated VL domains. Electron microscopy showed the oligomeric antibody to be predominantly dimers and trimers in which the monomeric units were associated through the tips of the Fab portion of the antibody, presumably through the protruding N-terminal VL domains. Similar examination of monomers demonstrated several molecular forms, including individual molecules with self-crosslinked Fab arms and others displaying the open Y and T shapes typically observed for IgG antibodies. The monomers also displayed distally protruding domain-like structures. The oligomers produced by this cell line therefore occurred through the noncovalent interaction between the extra light chain variable domains.

Manganese absorption and retention by young women is associated with serum ferritin concentration.

BACKGROUND: The interaction between iron and manganese in the gut is well characterized but iron status has not been shown to affect manganese absorption. OBJECTIVE: The objective of this study was to determine whether iron status as determined by serum ferritin concentrations affects manganese absorption, retention, balance, and status. DESIGN: The subjects were healthy young women; 11 had serum ferritin concentrations >50 microg/L and 15 had serum ferritin concentrations <15 microg/L. In a crossover design, subjects consumed diets that supplied either 0.7 or 9.5 mg Mn/d for 60 d. Manganese absorption and retention were assessed during the last 30 d of each dietary period by using an oral dose of 54Mn; balance was assessed simultaneously. RESULTS: Dietary manganese did not affect manganese status, but high serum ferritin depressed arginase activity. The interaction of ferritin status and dietary manganese affected 54Mn absorption and biological half-life. Absorption was greatest in subjects with low ferritin concentrations when they were consuming the low-manganese diet, and was least in subjects with high ferritin concentrations. Biological half-life was longest when subjects with high ferritin concentrations consumed the low-manganese diet, and was shortest in all subjects consuming the high-manganese diet. Manganese balance was only affected by the amount of manganese in the diet. CONCLUSIONS: These results show that iron status, as measured by serum ferritin concentration, is strongly associated with the amount of manganese absorbed from a meal by young women. When greater amounts of manganese are absorbed, the body may compensate by excreting manganese more quickly.

Sex affects manganese absorption and retention by humans from a diet adequate in manganese.

Men (n = 20) and women (n = 20) consuming a diet adequate in manganese were fed 0.037 mBq 54Mn in a test meal. Subjects were counted in a whole-body counter for 70 d to determine whole-body retention of 54Mn. Data from days 10 to 20 and from days 19 to 70 were analyzed by linear regression to calculate absorption and biological half-life. Men absorbed significantly less 54Mn than women, but the 54Mn absorbed had a longer half-life in men. Estimates of absorption were higher, and estimates of half-life were lower, when data from days 10 to 20 were used compared with days 19 to 70. There was a significant association between manganese absorption and plasma ferritin concentrations and between manganese absorption and biological half-life. We conclude that men and women differ in manganese metabolism and that such differences may be related to iron status. We also conclude that regression estimates of absorption determined by using whole-body retention curves depend on the portion of the data used.

Evaluation of nuclear magnetic resonance spectroscopy for determination of deuterium abundance in body fluids: application to measurement of total-body water in human infants.

Nuclear magnetic resonance (NMR) spectroscopy was used to quantitate abundance of 2H in body water of human infants. This method provides precise measurement of total-body water without the extensive sample preparation requirements of previously described methods for determination of 2H content in body fluids. 2H2O (1 g/kg body weight) was administered to infants and saliva and urine were collected for up to 5 h. An internal standard was added directly to the fluid specimen and 2H enrichment in water was measured by NMR spectroscopy. Working range of deuterium abundance was 0.04-0.32 atom %. Coefficients of variation for saliva samples at 0.20 atom % 2H was 1.97%. 2H content in urine and saliva water reached a plateau by 4 h after administration, and amounts in the two fluids were virtually identical. Mean total-body water determination for six infants was 58.3 +/- 5.8% of body weight (range 53-66%).

Areas with high concentrations of selenium in the soil and forage produce beef with enhanced concentrations of selenium.

Beef provides a significant portion of human dietary selenium (Se), and it is possible that modest portions of beef produced in areas with high-Se soil and forage could provide the entire Recommended Dietary Allowance (RDA) for Se. The present study has addressed the environmental conditions that resulted in the production of high-Se beef. One hundred and thirty-eight cull cows were obtained from 21 ranches in five distinct geographic regions that, on the basis of soil parent material, reports of Se deficiency, and previous soil and forage Se surveys, were likely to have high or low Se concentrations in the soil. Grass and soil samples were taken from ranch sites, and hair, whole blood, skeletal muscle, diaphragm muscle, and liver samples were obtained from the animals. Hair and whole blood samples were taken 1 day prior to shipping. Selenium concentrations of all samples were determined by hydride generation atomic absorption spectroscopy. Geographic origin affected Se content of all samples (p < 0.05). Selenium concentrations in soil (r = 0.53; p < 0.01) and grass (r = 0.63; p < 0.01) were correlated to Se content of skeletal muscle. Selenium concentrations in whole blood, diaphragm, hair, and liver also were significantly correlated to Se content of skeletal muscle (p < 0.01). Cows that received Se in mineral supplements did not have significantly higher concentrations of Se in sampled tissues (p > 0.05). Results of this study suggest that the greatest source of variation in Se content of bovine skeletal muscle was the geographic region from which the beef originated and not production or management practices. Results also demonstrated that a 100 g serving of high-Se beef could provide 100% of the RDA for Se.

Pathologic and clinical features influencing outcome of thin cutaneous melanoma: correlation with newly proposed staging system.

The incidence of malignant melanoma is increasing. Because of increased awareness, early recognition of malignant melanoma has become more common. In 1997, a new staging system for cutaneous melanoma was proposed, with reclassification of thin melanoma < 1 mm, with and without ulceration. This report evaluates the pathologic and clinical features of thin melanomas influencing recurrence and survival from a tertiary cancer center in an attempt to correlate findings with the proposed staging system. A review of the Roswell Park Cancer Institute tumor registry identified 352 patients with thin cutaneous melanomas (< 1.0 mm) seen during an 18-year period ending August 30, 1998. Overall survival was 93 and 87 per cent at 5 and 10 years, respectively. Disease-free survival was 94 and 93 per cent at 5 and 10 years, respectively. Local recurrence occurred in 3 per cent of patients, regional recurrence in 3 per cent, and metastatic disease in 3 per cent, for an overall recurrence of 7 per cent, with a median follow-up of 118 months. Only the presence of ulceration was a significant prognostic factor for recurrence by both univariate and multivariate analysis. Failure rates (any recurrence) by Clark levels I, II, and III/IV were 3, 5, and 10 per cent, respectively (P = 0.14). Failure rates by tumor thickness (mm), for 0.0-0.24, 0.25-0.49, 0.50-0.74, and 0.75-0.99 were 3, 4, 7, and 10 per cent, respectively (P = 0.49). Ten-year disease-free survival for ulceration versus no ulceration was 40 and 94 per cent, respectively (P < 0.0001). We conclude that thin cutaneous melanoma carries an excellent prognosis with appropriate treatment. Our findings support inclusion of ulceration in a new staging system. Lesions 0.76 to 0.99 mm and Clark level III and IV may warrant close observation as a separate subgroup.

Cancer-protective properties of high-selenium broccoli.

Selenium (Se) from high-Se garlic reduces the incidence of chemically induced mammary tumors, and Se from high-Se broccoli reduces colon cancer. However, the ability of Se from high-Se broccoli to protect against mammary cancer has not been tested. Also, the sprout form of broccoli contains many secondary plant compounds that are known to reduce cancer risk, but the anticarcinogenic activity of broccoli sprouts has not been investigated. The present studies examined the ability of high-Se broccoli or high-Se broccoli sprouts to protect against chemically induced mammary or colon cancer. In one experiment, Sprague--Dawley rats that consumed diets containing 3.0 microg of Se/g supplied as high-Se broccoli had significantly fewer mammary tumors than rats fed 0.1 microg of Se as selenite with or without the addition of regular broccoli. In the second experiment, Fisher F-344 rats fed 2.0 microg of Se/g of diet supplied as either high-Se broccoli florets or high-Se broccoli sprouts had significantly fewer aberrant colon crypts than rats fed 0.1 or 2 microg of Se/g of diet supplied as selenite with or without the addition of low-Se broccoli. These data demonstrate that the cancer-protective effect of Se in high-Se broccoli extends to mammary cancer and the protective forms of broccoli against colon cancer include high-Se broccoli sprouts.

Technological necessity of antioxidants in the food industry.

Antioxidants are one of the principal lines of defence in protecting quality as food or ingredients move from the farm through processing and distribution to the consumer. The urbanization of society and the resultant need to process complex, higher-quality foods have required that products survive a longer transportation time and an extended shelf-life. Consumers are also becoming more quality oriented and health conscious in their food selections. The food manufacturer, therefore, is faced with the challenge of supplying wholesome high-quality foods to the consumer. One of the major sources of change that occurs during processing, distribution and final preparation of foods is oxidation. Among the major food quality issues influenced by lipid oxidation are nutritional quality, toxicity, flavour, texture and colour. Antioxidants significantly extend the shelf-life of foods containing oxidizable lipids such as vegetable oils, animal fats, flavourings, spices, nuts, processed meats and snack products. It is important to note that oxidation and the need for antioxidants is not limited to high-fat foods, but includes cereals and other items that contain only small amounts of lipids.

New amino acid derivatives formed by alkaline treatment of proteins.

Intense heat treatment of proteins at high pH favors formation of transient, reactive intermediates derived from serine and cystine. The postulated dehydroalanine intermediate reacts further with the epsilon-amino groups side chains and sulfhydryl groups of cysteine residues to form derivatives of lysinoalanine and lanthionine. Recent studies indicate that besides these crosslinked products, several others are formed, by reaction of histidine, arginine, and possibly other residues. For this reason, caution should be exercised in assigning the prelysine peak(s) of an amino acid chromatogram to lysinoalanine. These results suggest that unnatural amino acid derivatives, other than lysinoalanine, may also contribute to the toxic effects reported from studies in which alkali-treated protein was fed to rats.

Reactions of proteins with dehydroalanines.

Reactions of proteins with dehydroalanine or derivatives of dehydroalanine were studied as models for protein crosslinking. Treatment of casein, bovine serum albumin, lysozyme, wool or polylysine with acetamido- and phenylacetamido acrylic acid methyl esters at pH 9-10 converted varying amounts of lysine to lysinoalanine residues. Howver, complete transformation was not achieved. Incomplete reaction is atributed to partial hydrolysis of the esters to the less reactive acrylic acids under the reaction conditions. Similar studies were made of the reactivities of protein SH groups generated by reduction of disulfide bonds by tributylphosphine. The SH groups could be completely alkylated at pH 7.6 in aqueous propanol, as shown by nearly quantitative recovery of lanthionine. Such a procedure might therefore be used to estimate cystine contents of proteins.

Inhibitory effect of mercaptoamino acids on lysino-alanine formation during alkali treatment of proteins.

Alkali treatment of food proteins converts some amino acid residues to the unnatural amino acid lysinoalanine which has been found to cause kidney damage when fed to rats. Formation of lysinoalanine was essentially prevented when isolates of soy protein and casein were exposed to alkali in the presence of thio-alamino acids such as cysteine. The results suggest that added thiols minimize the formation of potentially toxic lysinoalanine.

Manganese deficiency and toxicity: are high or low dietary amounts of manganese cause for concern?

Manganese is an essential trace element that is required for the activity of several enzymes. Manganese is also quite toxic when ingested in large amounts, such as the inhalation of Mn-laden dust by miners. This review examines Mn intake by way of the food supply and poses the question: Is there reason to be concerned with Mn toxicity or deficiency in free-living populations in North America? Although much remains to be learned of the functions of Mn, at present there are only a few vaguely described cases of Mn deficiency in the medical literature. Given the heterogeneity of the North American food supply, it is difficult to see the possibility of more than greatly isolated and unique instances of Mn deficiency. However, low Mn-dependent superoxide dismutase activity may be associated with cancer susceptibility, and deserves further study. There may be reasons, however, to be concerned about Mn toxicity under some very specialized conditions. Increasing numbers of young people are adopting a vegetarian lifestyle which may greatly increase Mn intake. Iron deficiency may increase Mn absorption and further increase the body-burden of Mn, especially in vegetarians. Mn is eliminated primarily through the bile, and hepatic dysfunction could depress Mn excretion and further contribute to the body burden. Would such a combination of events predispose substantial numbers of people to chronic Mn toxicity? At present, there is no definite proof of this occurring, but given the state of knowledge at the present time, more studies with longer time-frames and more sensitive methods of analysis are needed.

Selenium (Se) from high-selenium broccoli is utilized differently than selenite, selenate and selenomethionine, but is more effective in inhibiting colon carcinogenesis.

The reduction in incidence of chemically-induced colon cancer by foods high in selenium (Se) was investigated in Fisher-344 rats. The foods used were high-Se broccoli (produced in a greenhouse by addition of selenate to the media surrounding the plant roots) and a processed high-Se wheat product (made by milling high-Se wheat purchased from a seleniferous area). Weanling rats were fed diets containing different amounts of Se from these foods or from selenium salts (selenite and selenate). Early in the experiment the animals were injected with a chemical carcinogen. After 11 weeks on diets animals were killed and the colons examined for preneoplastic lesions (aberrant crypts foci, ACF). ACF were significantly reduced in animals fed supra-nutritional amounts of Se from broccoli, despite the finding that Se from broccoli was poorly bioavailable. Supra-nutritional amounts of Se from high-Se processed wheat also significantly reduced aberrant crypts (AC), although pure selenomethionine, (the predominant chemical form of Se in wheat), did not significantly reduce AC. These results emphasize the need to study Se in food forms, and not extrapolate from previous studies using pure chemical forms in cancer inhibition studies. They also demonstrate that foods with high Se bioavailability are not necessarily the most efficacious for cancer incidence reduction.

Effect of supranutritional and organically bound selenium on performance, carcass characteristics, and selenium distribution in finishing beef steers.

Dietary selenium influences the Se content in edible muscle of beef cattle. Limited data are available to describe the effects that feeds naturally high in Se have on production, carcass characteristics, and Se distribution in terminal tissues. Therefore, 43 crossbred steers (BW = 351 +/- 24 kg) were stratified by BW and assigned to one of four dietary treatments: Se adequate (CON; n = 12), Se provided as high-Se wheat (WHT; n = 9), high-Se hay (HAY; n = 11), or sodium selenate (SEO; n = 11). Daily selenium intake for WHT, HAY, and SEO diets was 65 microg/kg BW, whereas it was 9.5 microg/kg BW for CON. Diets were similar in ingredient composition (25% wheat, 39% corn, 25% grass hay, 5% desugared molasses, and 6% wheat middling-based supplement; DM basis), isonitrogenous and isocaloric (14.0% CP, 2.12 Mcal NEm/kg DM and 1.26 Mcal NEg/ kg DM), and offered once daily (1500) individually to steers in a Calan gate system for 126 d. At the end of the trial, steers were slaughtered; carcass data were recorded; and samples of the liver, kidney, spleen, semitendinosus, and hair were collected for Se analysis. Intake of DM, G:F, and ADG did not differ (P > 0.13). No differences (P > 0.12) were noted for hot carcass weight, organ weights, longissimus muscle area, back-fat thickness, marbling scores, or quality and yield grade. Kidney, pelvic, and heart fat tended to be higher (P = 0.06) in CON and WHT compared with SEO and HAY steers (2.9, 2.4, 2.5, 2.9 +/- 0.2% for CON, SEO, HAY, and WHT, respectively). Selenium concentrations in all tissues collected differed (P < 0.003) due to treatment. Distribution of Se to the kidney, spleen, and hair were similar with CON < SEO < HAY < WHT (8.40, 10.05, 10.86, 12.89 +/- 0.26 ppm for kidney; 2.00, 2.60, 3.82, 5.16 +/- 0.09 ppm for spleen; 1.80, 4.00, 5.93, 10.54 +/- 0.56 ppm for hair; P < 0.01). The distribution of Se in liver and muscle (DM basis) differed from that in other tissues, with CON < HAY < SEO = WHT (2.33, 6.56, 9.91, 10.79 +/- 0.80 ppm; P < 0.01) and CON = SEO < HAY < WHT (1.33, 1.55, 3.32, 4.41 +/- 0.18 ppm; P < 0.01), respectively. When providing dietary Se at supranutritional levels, source of Se did not affect production or carcass characteristics, but it altered the distribution and concentration of Se throughout the tissues of finishing beef steers.

Effect of high-selenium wheat on visceral organ mass, and intestinal cellularity and vascularity in finishing beef steers.

Twelve crossbred steers (351 +/- 24 kg initial BW) were used to determine effects of high-Se wheat on visceral tissue mass, intestinal cell growth, and intestinal cellularity and vascularity. Steers were allotted randomly by BW to one of two treatments consisting of 75% concentrate diets that supplied 1) adequate Se concentration (7 to 12 microg x kg x BW(-1) x d(-1)) or 2) high-Se concentration (60 to 70 microg x kg x BW(-1) x d(-1)). Diets were similar in composition, including 25% grass hay, 25% wheat, 39% corn, 5% desugared molasses, and 6% wheat middlings supplement on a DM basis. In the Se treatment, high-Se wheat (10 ppm Se, DM basis) was replaced with low-Se wheat (0.35 ppm Se, DM basis). Diets were formulated to be similar in CP and energy (14.0% CP, 2.12 Mcal of NEm/kg, and 1.26 Mcal NEg/kg of DM) and were offered daily (1500) to individual steers in an electronic feeding system. Diets were fed at 2.38% BW. After 126 d, steers were slaughtered, and individual visceral tissue weights determined. Concentrations of DNA, RNA, and protein of duodenum, ileum, and total small intestine were not affected (P > or = 0.33) by treatment. Similarly, RNA:DNA and protein:DNA ratios in duodenum, jejunum, ileum, and whole small intestine were not (P > or = 0.33) affected by feeding high-Se wheat. Conversely, jejunal weight was greater (P < 0.002) in steers fed high-Se wheat than in controls (916 vs. 1,427 +/- 84 g). Jejunal DNA was increased (P < 0.04) in steers fed high-Se wheat (2.95 vs. 3.56 +/- 0.19 mg/g), suggesting increased cell number. Concentrations of jejunal RNA and protein were not altered by treatment; however, because the jejunal weight increased in high-Se steers, DNA, RNA, and protein contents (grams) were greater than in control steers (P < 0.05). Vascularity of jejunal tissue decreased (P < 0.10) with high-Se wheat; however, because jejunal mass was greater for the high-Se wheat treatment, total microvascular volume was not affected by treatment. Percentage of jejunal crypt cell proliferation was not affected (P = 0.48) by treatment; however, total number of cells proliferating within the jejunum was increased in steers fed high-Se wheat. Data indicate that the lower jejunal vascularity in the diet high in Se (provided from wheat) may have resulted in increased jejunal mass to meet physiological nutrient demand. Therefore, negative effects of Se level used in this study on productive performance of feedlot steers are not expected.

Manganese uptake and release by cultured human hepato-carcinoma (Hep-G2) cells.

The liver is the primary organ involved in manganese (Mn) homeostasis. The human hepato-carcinoma cell line, Hep-G2, shows many liver specific functions. Consequently, Hep-G2 cells were investigated as a possible model of hepatic metabolism of Mn. Initial experiments showed that the concentration of Mn in the diet, or culture medium, similarly affected the retention of Mn by isolated rat hepatocytes and Hep-G2 cells. Manganese uptake by Hep-G2 cells suggested that uptake was followed by release from the cell. Uptake was saturable and half-maximal at 2.0 micromol Mn/L, and was inhibited by iodoacetate, vanadate, cold, and bepridil. The cations Fe2+, Cu2+, Ni2+, Cd2+, and Zn2+ decreased Mn uptake. Uptake was dependent on Calcium (Ca) concentration in a manner that resembled saturation kinetics. Cells that were pulsed with 54Mn and then placed into nonradioactive medium quickly released a large portion of their internalized Mn. Release of internalized Mn could be inhibited by low temperature, nocodozole, quinacrine and sodium azide. These data show that Hep-G2 cells are a potentially good model of hepatic Mn metabolism. Mn is taken up by a facilitated process that may be related to Ca uptake. Release apparently is an active, controlled process, that may involve microtubules and lysosomes.

Effect of sex and time of sampling on selenium and glutathione peroxidase activity in tissues of mature rats.

Sprague-Dawley rats were used to investigate variations in measures of glutathione peroxidase (GSH-Px) and selenium (Se) concentration resulting from diurnal cycles and sex. Mature rats (equal numbers of males and females) were killed at 4 h intervals over a 48 h period (0200, 0600, 1000, 1800 and 2200 h each day). Selenium and GSH-Px were measured in plasma, erythrocytes, and liver and kidney cytosols. Selenium concentrations did not vary diurnally, but plasma GSH-Px activities were higher during the light than dark periods. Males had greater plasma GSH-Px activities and Se concentrations (42 EU and .45 mg/kg, respectively) than females (35 EU and .41 mg/kg respectively). GSH-Px activities were also higher in male kidney cytosols than females (117 and 76 EU, respectively). Selenium and GSH-Px activities, however, were lower in male liver cytosols (.48 mg/kg and 272 EU) than females (1.19 mg/kg and 795 EU, respectively). These data suggest that Se is distributed differently in male and female rats and the difference in Se distribution is accomplished by differences in GSH-Px activities.

Manganese absorption and retention in rats is affected by the type of dietary fat.

There is evidence that manganese (Mn) metabolism may be altered by the form and amount of dietary fat. Also, iron (Fe) absorption is greater with saturated fats, as compared to polyunsaturated fatty acids (PUFAs). The absorption of Fe and Mn are interrelated in many aspects; therefore, the form of dietary fat may indirectly alter Mn absorption. The reported studies were conducted to determine whether saturated fat, as compared to unsaturated fat, affected Mn absorption, retention, and metabolism. In experiment I, adult rats were fed diets containing either 0.7 or 100.4 microg/g Mn with the fat source as high-linoleic safflower oil or stearic acid. After 2 wk of equilibration, the animals were fed a test meal of 54Mn followed by whole-body counting for 10 d. Manganese absorption was significantly (p < 0.05) lower in the stearic acid group (0.9-4.8%) than in the safflower oil group (20-33.8%); however, the biological half-life was shorter in the safflower oil group. Retention of 54Mn and total Mn was always significantly (p < 0.05) greater in the safflower oil group when dietary Mn was low, but it was the same when dietary Mn was high. In experiment II, weanling rats were fed 1.3, 39.3, or 174.6 microg Mn/g and either stearate, high-oleic safflower oil or high-linoleic safflower oil for 8 wk. Long-term feeding of the stearate and low Mn-containing diet resulted in a significant (p < 0.0001) reduction in heart superoxide dismutase activity and kidney and liver Mn concentrations compared to the other diets. These data show that stearic acid inhibitits Mn absorption, but it may not inhibit Mn retention when dietary Mn is high.