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PubMed1980

Palatability of sucrose-, sorbitol-, and saccharin-sweetened activated charcoal formulations.

The palatabilities of thickened activated charcoal formulations flavored with sucrose, sorbitol or saccharin sodium were compared. Three flavored activated charcoal formulations were prepared from a base of 25 g of activated charcoal, 1.5 g of carboxymethylcellulose, and 75 g of distilled water. The ratios of sweetener to activated charcoal were 1:1 for sucrose and sorbitol, and 1:20 for saccharin sodium. The palatabilities of the three flavored and one unflavored formulation were rated by 16 adults for taste, texture, ease of swallowing, and overall impression. No significant palatability differences were noted among the flavored mixtures, but all three flavored formulations were significantly more acceptable than the unflavored mixture (p less than 0.005). Saccharin sodium, sucrose, and sorbitol are suitable flavoring agents for activated charcoal slurries. Because saccharin sodium requires the smallest total volume to deliver a given quantity of activated charcoal, it has a distinct advantage over sucrose and sorbitol.

Adult↗
PubMed1999

Factors contributing to adverse soft tissue reactions due to the use of tartar control toothpastes: report of a case and literature review.

Tetrasodium and/or tetrapotassium pyrophosphate (Ppi) is the anticalculus component of most tartar control dentifrices on the market today. While pyrophosphates alone are not responsible for hypersensitivity reactions, several modifications which may lead to adverse oral manifestations may occur when pyrophosphates are added to a dentifrice. First, tetrasodium pyrophosphate in a dentifrice forms a slightly alkaline solution upon oral use which could irritate oral membranes. Second, increased concentrations of flavoring agents, known to be sensitizers, are needed to mask the strong bitter taste of pyrophosphates. Third, increased concentrations of detergents, capable of producing hypersensitivity reactions, are necessary to allow the pyrophosphates to become soluble in the dentifrice. Fourth, a pre-existing condition of reduced salivary flow may augment hypersensitivity to tartar control toothpastes. While pyrophosphates have been approved as additives in dentifrices, these compounds along with the increased concentrations of flavorings and detergents and their higher intraoral alkalinity are strongly implicated as the causative factor in certain hypersensitivity reactions.

Adult↗
PubMed2000

Vanillin as an antioxidant in rat liver mitochondria: inhibition of protein oxidation and lipid peroxidation induced by photosensitization.

Using rat liver mitochondria, as model systems, we have examined the ability of the natural compound and the food-flavoring agent, vanillin to protect membranes against oxidative damage induced by photosensitization at concentrations normally used in food preparations. Vanillin, at a concentration of 2.5 mmol/L, has afforded significant protection against protein oxidation and lipid peroxidation in hepatic mitochondria induced by photosensitization with methylene blue plus light. The effect observed was both time- and concentration-dependent. The inhibitory effect is similar to ascorbic acid and the singlet oxygen quencher, diazabicyclo[2.2.2]octane (DABCO) but less effective than sodium azide and glutathione. Examination of possible mechanisms responsible for the observed protection, showed that vanillin has a significant ability to quench singlet oxygen (1O2), a reactive species responsible for damage induced during photosensitization by Type II mechanism. Hence, this flavoring compound, due to its antioxidant ability, may have potential to prevent oxidative damage to membranes in mammalian tissues and thereby the ensuing diseased states.

Animals↗
PubMedDate not supplied

Oral midazolam-grapefruit juice drug interaction.

Oral midazolam is a frequently used sedative in pediatric dentistry. Although an oral form of midazolam is now commercially available, some practitioners continue to use the IV midazolam as an oral medication. If the injectible form of midazolam is administered orally, its bitter taste requires the use of a flavoring agent. Grapefruit juice is contraindicated for this purpose as it inhibits cytochrome P450 (CYP) 3A4. CYP 3A4 is located in the intestine and liver. Inhibition of this cytochrome results in delayed absorption and reduced first pass effect on midazolam. This results in increased blood plasma levels of midazolam of 56% and increased midazolam bioavailability of 35%. This can result in excessive levels of sedation for the pediatric patient. Grapefruit juice is therefore contraindicated for use with oral midazolam.

Administration, Oral↗
PubMed2004

Inhibition of peroxynitrite-mediated reactions by vanillin.

Several neurodegenerative diseases such as Alzeimer's and Parkinson's as well as septic shock and inflammation involve formation of reactive oxygen and nitrogen species that include peroxynitrite (PON). PON can also react with endogenous antioxidants. Therefore, dietary supplementation with antioxidants may help in these diseases. An exogenous antioxidant, vanillin (4-hydroxy-3-methoxybenzaldehyde), used widely as a food flavoring agent, was evaluated for its ability to scavenge PON and inhibit PON-mediated reactions. Nitration of tyrosine by PON was assessed by high-performance liquid chromatography (HPLC). This reaction was inhibited by vanillin. The oxidation of dihydrorhodamine 123 to fluorescent rhodamine 123 was also inhibited by vanillin. The kinetics of reaction between PON and vanillin was studied by stopped-flow technique. The products of this reaction were analyzed by HPLC, and hydroxyvanillin was identified as one of the five products with absorption at 350 nm. These data demonstrate that vanillin effectively scavenges PON in cell-free systems.

Antioxidants↗
PubMed1995

Determination of methyleugenol in rodent plasma by high-performance liquid chromatography.

A method has been developed and validated for the analysis of methyleugenol, a volatile flavoring agent, in rodent plasma at concentrations from 0.050 to 10.0 micrograms/ml. The method involves the addition of acetonitrile to the plasma, removal of the protein precipitate, and analysis of the supernatant by reversed-phase (C18) HPLC using an acetonitrile-water mixture with UV detection. The precision, accuracy, sensitivity, and specificity of the method were assessed. The stability of methyleugenol in plasma, during freeze-thaw cycles, refrigerated at the extract stage, and during the analysis was evaluated. The recovery of methyleugenol from plasma was also determined. This method was found to be acceptable for plasma concentrations in toxicokinetic studies of methyleugenol in rodents. Over 400 samples from toxicokinetic studies have been successfully analyzed to date. Kinetic data from a preliminary single administration intravenous and oral study in rats is also presented.

Acetonitriles↗
PubMed2006

Chavicol formation in sweet basil (Ocimum basilicum): cleavage of an esterified C9 hydroxyl group with NAD(P)H-dependent reduction.

Propenyl- and allyl-phenols, such as methylchavicol, p-anol and eugenol, have gained importance as flavoring agents and also as putative precursors in the biosynthesis of 9,9'-deoxygenated lignans, many of which have potential medicinal applications. In spite of several decades of investigation, however, the complete biosynthetic pathway to a propenyl/allylphenol had not yet been reported. We have subjected a Thai basil variety accumulating relatively large amounts of the simplest volatile allylphenol, methylchavicol, to in vivo administration of radiolabeled precursors and assays of protein preparations in vitro. Through these experiments, the biosynthesis of chavicol was shown to occur via the phenylpropanoid pathway to p-coumaryl alcohol. Various possibilities leading to deoxygenation of the latter were examined, including reduction of the side-chain double bond to form p-dihydrocoumaryl alcohol, followed by dehydration to afford chavicol, as well as formation of p-methoxycinnamyl alcohol, with further side-chain modification to afford methylchavicol. A third possibility studied was activation of the side-chain alcohol of p-coumaryl alcohol, e.g.via esterification, to form a more facile leaving group via reductive elimination. The latter was shown to be the case using p-coumaryl esters as potential substrates for a NAD(P)H-dependent reductase to afford chavicol, which is then O-methylated to afford methylchavicol.

Alcohols↗
PubMed1976

Hepatocarcinogenicity of estragole (1-allyl-4-methoxybenzene) and 1'-hydroxyestragole in the mouse and mutagenicity of 1'-acetoxyestragole in bacteria.

Approximately 20% of a dose of estragole, a naturally occurring flavoring agent, was excreted in the urine of outbred male CD -1 mice as a conjuage (presumably the glucuronide) of 1'-hydroxyestragole, Estragole and its 1'-hydroxy metabolite caused significant increases in the incidences of hepatocellular carcinomas in male CD-1 mice that received the compounds by sc injection at 1-22 days of age. Estragole induced hepatocellular carcinomas by 15 months in 23 and 39% of the mice that received total doses of 4.4 and 5.2 mumoles, respectively, and lived to an age of 12 months or more. Of the 12-month survivors given a total dose of 4.4 mumoles of 1'-hydroxyestragole, 70% developed hepatocellular carcinomas; the incidence in mice that received only the vehicle (trioctanoin) was 12%. Multiple tumors ocurred in 5, 28, 64, and 0%, respectively, of the mice in each of these 4 groups. Of the mice given a total dose of 4.4 mumoles of 1'-hydroxysafrole, 59developed hepatocellular carcinomas; 39% of the mice bore multiple liver tumors. As previsously demonstrated for 1'-acetoxysafrole, 1'-acetoxyestragole and 1'-acetoxy-1-allyl-4-methoxynaphthalene reacted nonenzymatically with guanosine and inosine to form adducts. These electrophilic esters were strongly mutagenic for the Salmonella typhimurium missense mutant TA100. 1'-Acetoxyallybenzene had little or no activity in either of these tests. Attempts to demonstrate liver-mediated mutagenicty for 1'-hydroxysafrole and 1'-hydroxyestragole in the bacterial test system were unsuccessful.

Allylbenzene Derivatives↗
PubMed1999

Long-term carcinogenicity of pan masala in Swiss mice.

Carcinogenicity of pan masala, a dry powdered chewing mixture of areca nut, catechu, lime, spices and flavoring agents was evaluated by means of the long-term animal bio-assay 6- to 7-week old male and female S/RVCri mice were divided randomly into intermediate and lifetime exposure groups and fed normal diet without pan masala-(zero dose) or diet containing 2.5% and 5% pan masala. Animals in the intermediate-exposure group (n = 10/gender/dose group) were killed after 6, 12 or 18 months of treatment, while those in the lifetime-exposure group (n = 54/gender/dose group) were killed when moribund or at the termination of the experiment at 24 months. Several tissues were processed for histopathological examination. The body weight and survival rate of mice fed pan masala were lower than that of the controls. Histopathological observations of tissues from control animals did not reveal any neoplastic alterations. However, lifetime feeding of pan masala induced adenoma of the liver, stomach, prostate and sebaceous glands, also forestomach papilloma, liver hamartoma, hepatoma and hemangioma, carcinoma of the forestomach, adenocarcinoma of the lung and liver, and testicular lymphoma. Neoplastic lesions appeared mainly in the liver (n = 13), stomach (n = 3) and lung (n = 8). Lung adenocarcinoma, the most frequent malignant tumor type, was observed in 2/120 mice in the intermediate-exposure group and in 8/216 animals in the lifetime-exposure group. Statistical analysis of tumor-induction data revealed a significant dose-related increase in lung adenocarcinomas but not in liver and stomach neoplasms indicating that lung is the major target tissue for the carcinogenic action of pan masala.

Animals↗
PubMed2005

Release of nucleotides and nucleosides during yeast autolysis: kinetics and potential impact on flavor.

Nucleotides, particularly 5'-nucleotides, are important flavoring agents found in many foods and beverages. Their precise effect on the flavor of wines aged on lees has not been examined previously. In this study nucleotides and nucleosides released by yeast during autolysis in a model wine system and in Champagne wines were identified and quantified, and their impact on wine flavor was determined. Ribonucleotides only were detected in yeast autolysate and in Champagne wines. In wines ribonucleotides were quantified by tandem mass spectrometry coupled to HPLC. The maximum concentration of total nucleotides was very low with a maximum of approximately 3 mg/L in wine aged on yeasts for 9 years. In young wines the most important nucleotide was 5'-UMP, but after 2 years of aging its concentration decreased and the concentration of 5'-GMP slowly increased. The threshold values of the most representative nucleotides in Champagne wines were higher than the concentrations found in the same wines. However, it is known that there is synergism between the different nucleotides and also in the presence of glutamic acid. This phenomenon could explain the difference observed in descriptive profiles of wines spiked with nucleotides.

DNA, Fungal↗
PubMedDate not supplied

Quantitation of volatile oils in ground cumin by supercritical fluid extraction and gas chromatography with flame ionization detection.

Ground cumin is used as a flavoring agent in a number of ethnic cuisines. The chemical entities, which primarily establish its characteristically pungent flavor, are found in the volatile oil of cumin. Fixed oils and carbohydrates tend to round out the harshness of the volatile oil components. However, the quantity of volatile oil is commonly the measure of the quality of this spice. For several decades, the spice industry has used a classical distillation procedure for the determination of volatile oil in cumin and other spices. However, the method is cumbersome and requires nearly 8 h to complete. Supercritical fluid extraction with capillary gas chromatography-flame ionization detection is utilized in the formulation of a rapid, accurate, and specific method for the determination of volatile oil in ground cumin. Samples are extracted in a static-dynamic mode with CO2 at 550 bar and 100 degrees C. Toluene is used as a static modifier addition. The extracted volatile oil, collected in toluene, is analyzed directly using tetradecane as the internal standard. Integration is performed as grouped peaks to include all chemical entities found in cumin volatile oil recovered from the official distillation procedure. Results from this procedure compare favorably with those obtained by the official procedure (coefficient of correlation = 0.995, 24 samples).

Chromatography, Gas↗
PubMed2003

Safety assessment of Salicylic Acid, Butyloctyl Salicylate, Calcium Salicylate, C12-15 Alkyl Salicylate, Capryloyl Salicylic Acid, Hexyldodecyl Salicylate, Isocetyl Salicylate, Isodecyl Salicylate, Magnesium Salicylate, MEA-Salicylate, Ethylhexyl Salicylate, Potassium Salicylate, Methyl Salicylate, Myristyl Salicylate, Sodium Salicylate, TEA-Salicylate, and Tridecyl Salicylate.

Salicylic Acid is an aromatic acid used in cosmetic formulations as a denaturant, hair-conditioning agent, and skin-conditioning agent--miscellaneous in a wide range of cosmetic products at concentrations ranging from 0.0008% to 3%. The Calcium, Magnesium, and MEA salts are preservatives, and Potassium Salicylate is a cosmetic biocide and preservative, not currently in use. Sodium Salicylate is used as a denaturant and preservative (0.09% to 2%). The TEA salt of Salicylic Acid is used as an ultraviolet (UV) light absorber (0.0001% to 0.75%). Several Salicylic Acid esters are used as skin conditioning agents--miscellaneous (Capryloyl, 0.1% to 1%; C12-15 Alkyl, no current use; Isocetyl, 3% to 5%; Isodecyl, no current use; and Tridecyl, no current use). Butyloctyl Salicylate (0.5% to 5%) and Hexyldodecyl Salicylate (no current use) are hair-conditioning agents and skin-conditioning agents--miscellaneous. Ethylhexyl Salicylate (formerly known as Octyl Salicylate) is used as a fragrance ingredient, sunscreen agent, and UV light absorber (0.001% to 8%), and Methyl Salicylate is used as a denaturant and flavoring agent (0.0001% to 0.6%). Myristyl Salicylate has no reported function. Isodecyl Salicylate is used in three formulations, but no concentration of use information was reported. Salicylates are absorbed percutaneously. Around 10% of applied salicylates can remain in the skin. Salicylic Acid is reported to enhance percutaneous penetration of some agents (e.g., vitamin A), but not others (e.g., hydrocortisone). Little acute toxicity (LD(50) in rats; >2 g/kg) via a dermal exposure route is seen for Salicylic Acid, Methyl Salicylate, Tridecyl Salicylate, and Butyloctyl Salicylate. Short-term oral, inhalation, and parenteral exposures to salicylates sufficient to produce high blood concentrations are associated primarily with liver and kidney damage. Subchronic dermal exposures to undiluted Methyl Salicylate were associated with kidney damage. Chronic oral exposure to Methyl Salicylate produced bone lesions as a function of the level of exposure in 2-year rat studies; liver damage was seen in dogs exposed to 0.15 g/kg/day in one study; kidney and liver weight increases in another study at the same exposure; but no liver or kidney abnormalities in a study at 0.167 g/kg/day. Applications of Isodecyl, Tridecyl, and Butyloctyl Salicylate were not irritating to rabbit skin, whereas undiluted Ethylhexyl Salicylate produced minimal to mild irritation. Methyl Salicylate at a 1% concentration with a 70% ethanol vehicle were irritating, whereas a 6% concentration in polyethylene glycol produced little or no irritation. Isodecyl Salicylate, Methyl Salicylate, Ethylhexyl (Octyl) Salicylate, Tridecyl Salicylate, and Butyloctyl Salicylate were not ocular irritants. Although Salicylic Acid at a concentration of 20% in acetone was positive in the local lymph node assay, a concentration of 20% in acetone/olive oil was not. Methyl Salicylate was negative at concentrations up to 25% in this assay, independent of vehicle. Maximization tests of Methyl Salicylate, Ethylhexyl Salicylate, and Butyloctyl Salicylate produced no sensitization in guinea pigs. Neither Salicylic Acid nor Tridecyl Salicylate were photosensitizers. Salicylic Acid, produced when aspirin is rapidly hydrolyzed after absorption from the gut, was reported to be the causative agent in aspirin teratogenesis in animals. Dermal exposures to Methyl Salicylate, oral exposures to Salicylic Acid, Sodium Salicylate, and Methyl Salicylate, and parenteral exposures to Salicylic Acid, Sodium Salicylate, and Methyl Salicylate are all associated with reproductive and developmental toxicity as a function of blood levels reached as a result of exposure. An exposure assessment of a representative cosmetic product used on a daily basis estimated that the exposure from the cosmetic product would be only 20% of the level seen with ingestion of a "baby" aspirin (81 mg) on a daily basis. Studies of the genotoxic potential of Salicylic Acid, Sodium Salicylate, Isodecyl Salicylate, Methyl Salicylate, cosmetic product would be only 20% of the level seen with ingestion of a "baby" aspirin (81 mg) on a daily basis. Studies of the genotoxic potential of Salicylic Acid, Sodium Salicylate, Isodecyl Salicylate, Methyl Salicylate, Ethylhexyl (Octyl) Salicylate, Tridecyl Salicylate, and Butyloctyl Salicylate were generally negative. Methyl Salicylate, in a mouse skin-painting study, did not induce neoplasms. Likewise, Methyl Salicylate was negative in a mouse pulmonary tumor system. In clinical tests, Salicylic Acid (2%) produced minimal cumulative irritation and slight or no irritation(1.5%); TEA-Salicylate (8%) produced no irritation; Methyl Salicylate (>12%) produced pain and erythema, a 1% aerosol produced erythema, but an 8% solution was not irritating; Ethylhexyl Salicylate (4%) and undiluted Tridecyl Salicylate produced no irritation. In atopic patients, Methyl Salicylate caused irritation as a function of concentration (no irritation at concentrations of 15% or less). In normal skin, Salicylic Acid, Methyl Salicylate, and Ethylhexyl (Octyl) Salicylate are not sensitizers. Salicylic Acid is not a photosensitizer, nor is it phototoxic. Salicylic Acid and Ethylhexyl Salicylate are low-level photoprotective agents. Salicylic Acid is well-documented to have keratolytic action on normal human skin. Because of the possible use of these ingredients as exfoliating agents, a concern exists that repeated use may effectively increase exposure of the dermis and epidermis to UV radiation. It was concluded that the prudent course of action would be to advise the cosmetics industry that there is a risk of increased UV radiation damage with the use of any exfoliant, including Salicylic Acid and the listed salicylates, and that steps need to be taken to formulate cosmetic products with these ingredients as exfoliating agents so as not to increase sun sensitivity, or when increased sun sensitivity would be expected, to include directions for the daily use of sun protection. The available data were not sufficient to establish a limit on concentration of these ingredients, or to identify the minimum pH of formulations containing these ingredients, such that no skin irritation would occur, but it was recognized that it is possible to formulate cosmetic products in a way such that significant irritation would not be likely, and it was concluded that the cosmetics industry should formulate products containing these ingredients so as to be nonirritating. Although simultaneous use of several products containing Salicylic Acid could produce exposures greater than would be seen with use of baby aspirin (an exposure generally considered to not present a reproductive or developmental toxicity risk), it was not considered likely that consumers would simultaneously use multiple cosmetic products containing Salicylic Acid. Based on the available information, the Cosmetic Ingredient Review Expert Panel reached the conclusion that these ingredients are safe as used when formulated to avoid skin irritation and when formulated to avoid increasing the skin's sun sensitivity, or, when increased sun sensitivity would be expected, directions for use include the daily use of sun protection.

Administration, Inhalation↗
PubMed1982

How sensory properties of foods affect human feeding behavior.

The sensory properties of food which can lead to a decrease in the pleasantness of that food after it is eaten, and to enhanced food intake if that property of the food is changed by successive presentation of different foods, were investigated. After eating chocolates of one color the pleasantness of the taste of the eaten color declined more than of the non-eaten colors, although these chocolates differed only in appearance. The presentation of a variety of colors of chocolates, either simultaneously or successively, did not affect food intake compared with consumption of the subject's favorite color. Changes in the shape of food (which affects both appearance and mouth feel) were introduced by offering subjects three successive courses consisting of different shapes of pasta. Changes in shape led to a specific decrease in the pleasantness of the shape eaten and to a significant enhancement (14%) of food intake when three shapes were offered compared with intake of the subject's favorite shape. Changes in just the flavor of food (i.e., cream cheese sandwiches flavored with salt, or with the non-nutritive flavoring agents lemon and saccharin, or curry) led to a significant enhancement (15%) of food intake when all three flavors were presented successively compared with intake of the favorite. The experiments elucidate some of the properties of food which are involved in sensory specific satiety, and which determine the amount of food eaten.

Adolescent↗
PubMed1995

Pharmacokinetics of active drug metabolites after oral administration of perillyl alcohol, an investigational antineoplastic agent, to the dog.

The monocyclic terpene d-limonene, a major component in many citrus essential oils (1-3), has been used for many years as a flavoring agent, food additive, and fragrance (1, 2). It was recently demonstrated that limonene exhibits both chemopreventive and therapeutic effects against chemically induced mammary tumors in rats (4-10). Mechanistic studies revealed that limonene inhibits the posttranslational isoprenylation of 21-26 kDa cellular proteins implicated in cell growth and proliferation (11-13). Limonene is extensively metabolized by a variety of mammalian species (14-17). Its principal circulating metabolites identified in the rat, perillic acid and dihydroperillic acid, are also effective inhibitors of isoprenylation and cellular proliferation in vitro (17, 18). Furthermore, one of the metabolic precursors of these compounds, perillyl alcohol (16), is considerably more potent than limonene against the in vivo rat mammary tumor models (19). A preliminary report of an ongoing phase I clinical trial with limonene indicated that a single oral dose of 100 mg/kg is well tolerated (20). However, an extrapolation based upon the rat mammary tumor regression studies suggests that the minimum human dose requirement would be 1000 mg/kg/ day (6). The administration of such a large dose, which amounts to more than 80 ml of an oily volatile liquid, on a continuing basis may cause problems. Thus, perillyl alcohol is currently being developed as a clinical candidate at the National Cancer Institute because of its greater potency than limonene, which may enable potentially effective systemic concentrations of the active principals to be achieved at considerably lower doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1976

Improved taste acceptability for an oral hyperalimentation dosage form.

Various flavoring agents were evaluated as to their ability to improve the taste acceptability of Vivovnex-HN, a potent oral hyperalimentation diet. Several imitation flavors were incorporated into the Vivonex-HN powder in different concentrations with and without an artificial sweetener. The mixtures were rated by a taste panel. Among the unsweetened flavors, spray-dried orange juice, Sealva imitation mint No.381 and cherry mint imitation appeared to be the most acceptable flavors. Among the individual flavors sweetened with 0.025% sodium saccharin, rum, strawberry and raspberry proved to be the most acceptable. Among all of the formulations studied, a combination of rum, strawberry and raspberry with 0.025% sodium saccharin was found to be optimal.

Administration, Oral↗
PubMed1996

Inhibition of tumor promotion in SENCAR mouse skin by ethanol extract of Zingiber officinale rhizome.

There is considerable emphasis on identifying potential chemopreventive agents present in food consumed by the human population. Ginger rhizome (Zingiber officinale), known commonly as ginger, is consumed worldwide in cookeries as a spice and a flavoring agent. In prior in vitro studies, it has been shown that the water or organic solvent extract of ginger possesses antioxidative and antiinflammatory properties. In this study, we evaluated whether ethanol extract of ginger (GE) possesses anti-tumor-promoting effects in a mouse skin tumorigenesis model. Because skin tumor promoters induced epidermal ornithine decarboxylase (ODC), cyclooxygenase, and lipoxygenase activities, and edema and hyperplasia are conventionally used markers of skin tumor promotion, first, we assessed the effect of GE on these parameters. Preapplication of GE onto the skin of SENCAR mice resulted in significant inhibition of 12-0-tetradecanoylphorbol-13-acetate (TPA)-caused induction of epidermal ODC, cyclooxygenase, and lipoxygenase activities and ODC mRNA expression in a does-dependent manner. Preapplication of GE to mouse skin also afforded significant inhibition of TPA-caused epidermal edema (56%) and hyperplasia (44%). In long-term tumor studies, topical application of GE 30 min prior to that of each TPA application to 7,12-dimethylbenz(a)anthracene-initiated SENCAR mice resulted in a highly significant protection against skin tumor incidence and its subsequent multiplicity. The animals pretreated with GE showed substantially lower tumor body burdens compared with non-GE-treated controls. The results of our study, for the first time, provide clear evidence that GE possesses anti-skin tumor-promoting effects, and that the mechanism of such effects may involve inhibition of tumor promoter-caused cellular, biochemical, and molecular changes in mouse skin.

Administration, Cutaneous↗