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Biomedical subjects

L W Wattenberg

Publications and source records attributed to L W Wattenberg.

At least 37 records · Page 2Linked to original sources
PubMed1991

Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone carcinogenesis in mice by D-limonene and citrus fruit oils.

The effects of D-limonene and citrus fruit oils, i.e. orange oil and lemon oil, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced neoplasia of the lungs and forestomach of female A/J mice were investigated. D-Limonene and the citrus fruit oils given p.o. 1 h prior to NNK, also administered p.o., inhibited pulmonary adenoma formation and the occurrence of forestomach tumors. In an additional experiment, D-limonene given p.o. 1 h prior to NNK administered i.p. again showed pronounced inhibition of pulmonary adenoma formation. This study provides additional data demonstrating that non-nutrient constituents of the diet can inhibit carcinogen-induced neoplasia when administered at a short time interval prior to carcinogen challenge.

Adenoma↗
PubMed1991

Inhibition of azoxymethane-induced neoplasia of the large bowel by 3-hydroxy-3,7,11-trimethyl-1,6,10-dodecatriene (nerolidol).

The inhibitory capacities of four terpenes on azoxymethane (AOM)-induced neoplasia of the large bowel and duodenum was studied in male F344 rats. A complete course of AOM administrations was given and 3 days later the rats were fed a semipurified diet containing 5 mg/g of the test compounds, i.e. 3-hydroxy-3,7,11-trimethyl-1,6,10-dodecatriene (nerolidol), beta-citronellol, (+/-)-linalool and (1R,2S,5R)-(-)-menthol or a corresponding control diet. The experiment was terminated 22 weeks after the last dose of AOM. Under these conditions, nerolidol showed an inhibitory effect on carcinogenesis of the large bowel. The number of rats bearing large bowel neoplasms (adenomas) was reduced from 82% in the controls to 33% in rats fed nerolidol and the number of tumors/rat from 1.5 in the controls to 0.7 in the nerolidol group. A reduction in adenocarcinomas of the duodenum was found but the data are not statistically significant. The effects of nerolidol are of interest in terms of the identification of a new inhibitor of carcinogenesis of the large bowel. The chemical structure of nerolidol suggests the possibility that the compound might have an impact on protein prenylation or some other aspect of the mevalonate pathway, but this remains to be established.

Animals↗
PubMed1990

Long term effects of benzo(a)pyrene on the activity of NAD(P)H:quinone reductase in the forestomach and glandular stomach of ICR/Ha mice.

The present study is part of an effort to identify biomarkers for various stages of preneoplasia. For this purpose, quinone reductase [NAD(P)H:quinone oxidoreductase, EC 1.6.99.2] (QR) activity in the forestomach of ICR/Ha mice was investigated at successive time points during benzo(a)pyrene (BP)-induced carcinogenesis. Six mg of BP in 0.2 ml of cottonseed oil or cottonseed oil alone were given orally twice a week for 2 weeks to female ICR/Ha mice. Ten mice from each group were sacrificed sequentially at 2-week intervals, and the QR activity was determined in the forestomach, a target tissue for BP carcinogenicity, and also in the glandular stomach, a non-target tissue. QR was significantly increased in the cytosolic, microsomal, and mitochondrial fractions of the forestomach of BP-treated animals. There was no significant increase in this activity in any fraction of the glandular stomach. The increases in QR activity in the subcellular fractions of the forestomach from BP-treated animals showed a two-surge pattern. The first was manifested at 2 weeks. The second, found at week 6, continued throughout the remaining course of the experiment. To our knowledge, the time course of changes in QR activity in the three subcellular fractions of mouse forestomach during BP carcinogenesis has not been demonstrated previously.

Animals↗
PubMed1990

Inhibition of carcinogenesis by naturally-occurring and synthetic compounds.

A continuing study of chemopreventive agents has focused on three categories of naturally-occurring compounds that inhibit carcinogen activation and are effective in preventing carcinogen-induced neoplasia when administered at short time intervals prior to carcinogen challenge. The three are: aromatic isothiocyanates found in cruciferous vegetables, monoterpenes from citrus fruits and caraway seed oils, and organosulfur compounds occurring in Allium species. The short time-interval effects could be significant in terms of their impact on responses of humans to carcinogen exposures. The capacity of sodium cyanate, cruciferous vegetables, orange oil, benzyl isothiocyanate, and D-limonene to act as both blocking and suppressing agents has been discussed. Two possible mechanisms for this multiphase activity were presented. The first is that these inhibitory substances activate a complex integrated defense mechanism against toxic compounds which entails both blocking and suppressing components. The blocking component is the initial line of defense, and the suppressing component constitutes a "fail-safe" backup to assure that if any of the toxic material attacks cellular constituents, its effects will be nullified. The second possible mechanism considered is that the inhibitors, because of high reactivity, have multiple biological effects that are separate and not part of a single, coordinated response. Inhibitors that have both blocking and suppressing effects could be particularly useful as chemopreventive agents.

Animals↗
PubMed1990

Inhibition of carcinogenesis by minor anutrient constituents of the diet.

A continuing study of chemopreventive agents has focused on several categories of naturally occurring compounds that inhibit carcinogen activation and are effective in preventing carcinogen-induced neoplasia when administered at short time-intervals before carcinogen challenge. The inhibitory compounds are: aromatic isothiocyanates found in cruciferous vegetables, monoterpenes present in citrus fruits and caraway-seed oil, and organosulphur compounds occurring in Allium species. Preliminary work indicates that glucobrassicin and indoles existing in cruciferous vegetables also have these attributes. Almost all carcinogens that are consumed in food require metabolic activation. Thus, inhibition of carcinogen activation reactions could be effective against this type of exposure. In addition, three naturally occurring compounds, i.e. phenethyl isothiocyanate, D-limonene and dipropyl sulphide inhibit activation of the tobacco-specific carcinogen NNK, and accordingly may have the capacity to diminish carcinogenic response to exposures to tobacco. The property of cruciferous vegetables, orange oil, benzyl isothiocyanate, and D-limonene, to act as both blocking and suppressing agents has been discussed. Two possible mechanisms for this multi-phase activity were presented. The first is that these inhibitory substances activate a complex integrated defence mechanism against toxic compounds which entails both blocking and suppressing components. The blocking component is the initial line of defence, and the suppressing component constitutes a 'fail-safe' backup to assure that if any of the toxic material attacks cellular constituents, its effects will be nullified. The second possible mechanism considered is that the inhibitors, because of high reactivity, have multiple biological effects that are separate and not part of a single, coordinated response. Inhibitors that have both blocking and suppressing effects could be particularly useful as chemopreventive agents. A simple interim classification of foods in terms of their potential impact on the occurrences of cancer has been proposed.

Allium↗
PubMed1989

Inhibition of N-nitrosodiethylamine carcinogenesis in mice by naturally occurring organosulfur compounds and monoterpenes.

Naturally occurring compounds belonging to two chemical groups were studied for their capacities to inhibit N-nitrosodiethylamine (NDEA)-induced carcinogenesis in female A/J mice. One group consists of organosulfur compounds found in Allium species, including garlic, onions, leeks, and shallots, and the other, two monoterpenes, i.e., D-limonene and D-carvone. In an initial experiment, in which organosulfur compounds were investigated, diallyl disulfide, allyl mercaptan, and allyl methyl disulfide were found to produce a marked inhibition of NDEA-induced neoplasia of the forestomach when the test compounds were administered p.o. 96 and 48 h prior to NDEA. The most potent was diallyl disulfide which reduced forestomach tumor formation by more than 90%. Pulmonary adenoma formation also was inhibited but to a considerably lesser extent, i.e., about 30%. In three additional experiments, test compounds were given p.o. either 15 min or 1 h prior to NDEA. Under these conditions diallyl disulfide and allyl mercaptan again inhibited forestomach tumor formation substantially, i.e., greater than 75%, and pulmonary adenoma formation marginally, i.e., less than 20%. In these experiments D-limonene and D-carvone were tested and reduced forestomach tumor formation by slightly over 60% and pulmonary adenoma formation by about 35%. The results of these studies provide evidence of an increasing diversity of naturally occurring compounds having the capacity to inhibit nitrosamine carcinogenesis.

Allium↗
PubMed1989

A case-control study of pancreatic cancer and cigarettes, alcohol, coffee and diet.

A pancreatic cancer case-control study was conducted in the Minneapolis-St. Paul area. Family members were interviewed about the subject's usage of cigarettes, alcohol, coffee, and other dietary factors in the two years prior to death (cases, n = 212) or prior to interview (controls, n = 220). The adjusted odds ratio for two packs or more of cigarettes per day was 3.92 (95% CI = 1.18, 13.01) and four or more drinks per day OR 2.69 (95% CI = 1.00, 7.27). Coffee was not a risk factor (seven cups or more per day; OR 0.58 (95% CI = 0.27, 1.27). A positive trend was observed for beef and pork consumption, and a negative trend from cruciferous vegetables.

Adult↗
PubMed1988

Inhibition of beta-propiolactone-induced neoplasia of the forestomach and large bowel by 4-mercaptobenzene sulfonate in mice and rats.

Studies have been initiated to find compounds that can trap direct-acting carcinogens within the lumen of the gastrointestinal tract and thus prevent these carcinogens from attacking tissues of the host. Sodium 4-mercaptobenzene sulfonate (4-MBSNa) is a potent nucleophile and was found to react rapidly in vitro with the direct-acting carcinogen beta-propiolactone (BPL). In further investigations 4-MBSNa was shown to inhibit mutagenesis resulting from exposure of Salmonella typhimurium strain TA-100 to BPL and a second direct-acting carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine. Subsequent experiments were performed to determine if 4-MBSNa would inhibit BPL-induced carcinogenesis in vivo. In the first of these, 4-MBSNa was administered by p.o. intubation to female A/J mice 5 min before p.o. administration of BPL. Under these conditions inhibition of carcinogenesis of the forestomach occurred. In a second experiment, 4-MBSNa was given by rectal intubation 5 min before BPL also administered intrarectally. Administration of BPL intrarectally produced adenomatous polyps of the large intestine. The occurrence of these neoplasms was inhibited by the prior administration of 4-MBSNa. The data presented show that 4-MBSNa has the capacity to trap direct-acting carcinogens and to inhibit the occurrence of BPL-induced neoplasia.

Animals↗
PubMed1988

Effects of organosulfur compounds from garlic and onions on benzo[a]pyrene-induced neoplasia and glutathione S-transferase activity in the mouse.

In the present study, eight organosulfur compounds from garlic and onions were studied for their inhibitory effects on benzo[a]pyrene (BP)-induced neoplasia of forestomach and lung of female A/J mice when administered 96 and 48 h prior to carcinogen challenge. These compounds had one, two or three linearly connected sulfur atoms. They included the four allyl group-containing derivatives: allyl methyl trisulfide (AMT), allyl methyl disulfide (AMD), diallyl trisulfide (DAT), and diallyl sulfide (DAS), and also four corresponding saturated compounds in which propyl groups were substituted for the allyl groups. All four allylic compounds inhibited BP-induced neoplasia of the forestomach. The saturated analogs were almost without inhibitory activity, indicating the importance of the allyl groups. DAT, which contains two allyl groups, was more potent than AMT, which contains only one allyl group, thus providing further evidence for the role of allyl groups in the inhibitory effects observed. DAS and AMD, but not DAT or AMT, inhibited pulmonary adenoma formation. The fact that in the lung the monosulfide and disulfide inhibited, but the trisulfide did not inhibit, indicates that the number of sulfur atoms in the molecule can control the organ sites at which protection against carcinogenesis will occur. All four allylic compounds induced increased glutathione S-transferase (GST) activity in the forestomach, but varied in their capacity to induce GST in lung, liver and small bowel. Their saturated analogs produced little or no induction. In evaluating relationships between diet and cancer, it would be useful to consider the possible role of garlic and onion organosulfur compounds as protective agents. In addition, further studies of this class of chemicals might lead to the identification and development of useful new chemopreventive compounds.

Allium↗
PubMed1987

Inhibition of beta-propiolactone-induced mutagenesis and neoplasia by sodium thiosulfate.

Studies have been initiated to find compounds that can trap direct-acting carcinogens within the stomach. Sodium thiosulfate (STS) is a potent nucleophile and in initial experiments was found to inhibit mutagenesis resulting from exposure of Salmonella typhimurium strain TA100 to the direct-acting carcinogens beta-propiolactone and styrene oxide. In in vitro experiments STS was shown to maintain its nucleophilicity in the acid pH range. It reacted with beta-propiolactone as rapidly at pH 2 as at pH 7.4. Thus STS has the prerequisite attributes to inhibit the carcinogenic effects of electrophiles in the stomach. Experiments were performed in which STS was administered by p.o. intubation to female A/J mice 5 min before p.o. administration of beta-propiolactone. Under these conditions, inhibition of formation of the forestomach tumors occurred. The data obtained suggest that use of nucleophiles to protect against direct-acting carcinogens is a potential strategy for chemoprevention.

Animals↗
PubMed1987

Effects of derivatives of kahweol and cafestol on the activity of glutathione S-transferase in mice.

The coffee constituents cafestol and kahweol are inducers of the activity of the detoxifying enzyme, glutathione S-transferase in laboratory animals. The two active functional groups, furan and glycol, on opposite ends of the diterpene nucleus of these two compounds have been modified. The resulting derivatives were evaluated for their ability to induce glutathione S-transferase activity in different tissues of the ICR/Ha mice. Derivatives of both cafestol and kahweol, which were the products of the modifications on the glycol function, retained much of the inducing properties of the parent compounds in the liver and mucosa of the small bowel. The effects of these compounds on the tissue acid-soluble sulfhydryl level, in general, were similar to those of the parent compounds. Some derivatives of kahweol, however, appeared to have lost their ability to induce increased levels of sulfhydryls in the liver. Catalytic hydrogenation of the furan moiety gave two products, the dihydro and tetrahydro derivatives. Both compounds and their corresponding acetates lost their effectiveness as inducers of glutathione S-transferase activity. In contrast, these compounds still retained their ability to induce increased levels of acid-soluble sulfhydryls in both the liver and the mucosa of the small bowel. These findings indicate that the furan moiety of cafestol and kahweol is vital to their biological activity as inducers of increased glutathione S-transferase activity.

Animals↗
PubMed1987

Inhibitory effects of benzyl isothiocyanate administered shortly before diethylnitrosamine or benzo[a]pyrene on pulmonary and forestomach neoplasia in A/J mice.

The inhibitory effects of benzyl isothiocyanate, a naturally-occurring constituent of cruciferous vegetables, on carcinogenesis of the forestomach and lungs of female A/J mice given dimethylnitrosamine (DEN) or benzo[a]pyrene (BP) was investigated. When administered by gavage 15 min prior to p.o. carcinogen challenge, benzyl isothiocyanate almost completely inhibited forestomach tumor formation resulting from DEN but had no effect on pulmonary tumor formation. With BP as the carcinogen, benzyl isothiocyanate had inhibitory effects on carcinogenesis of both the forestomach and lungs, the latter being greater. The implications for epidemiology studies and for chemopreventive strategies of compounds that inhibit when administered shortly before carcinogen challenge are discussed.

Animals↗
PubMed1986

Effects of allyl methyl trisulfide on glutathione S-transferase activity and BP-induced neoplasia in the mouse.

Allyl methyl trisulfide (AMT), a constituent of garlic oil, was studied for its effects on glutathione S-transferase (GST) activity and on benzo[a]pyrene (BP)-induced neoplasia of the forestomach and lungs of female A/J mice. AMT induced increased GST activity in the forestomach, small bowel mucosa, liver, and lung. The forestomach and small bowel mucosa responded to a single low dose of AMT (3.0 mumol) given by oral intubation, whereas liver and lung were less reactive. A dose schedule of two administrations of 15 mumol AMT given 48 hours apart gave close-to-maximum induction in all four tissues and was chosen for investigation of its inhibitory effects. With this dose schedule, AMT produced an inhibition of BP-induced neoplasia of the forestomach as shown by a greater than 70% reduction in the number of tumors found at the completion of the experiment. Inhibition of pulmonary neoplasia did not occur. AMT is a member of a new class of naturally occurring chemicals that have the capacity to inhibit chemical carcinogenesis.

Allyl Compounds↗
PubMed1986

Inhibitory effects of 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (Oltipraz) on carcinogenesis induced by benzo[a]pyrene, diethylnitrosamine and uracil mustard.

5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (Oltipraz) was studied for its capacity to inhibit carcinogen-induced neoplasia in female ICR/Ha mice. When administered by oral intubation 48 h prior to benzo[a]pyrene (BP), also given by oral intubation, Oltipraz inhibited the occurrence of pulmonary adenomas and tumors of the forestomach. The ratio of the number of tumors occurring in the mice receiving Oltipraz to that of the corresponding controls was: lung, 0.36 and forestomach 0.38. Inhibition also occurred when Oltipraz was given p.o. 24 h prior to BP. In other experiments, oral administration of Oltipraz 48 h prior to p.o. administration of diethylnitrosamine or uracil mustard inhibited pulmonary adenoma formation but to a lesser extent than with BP as the carcinogen. The low toxicity of Oltipraz found previously, coupled with evidence of protective effects against chemically diverse carcinogens, suggests that this compound should be studied further for its possible use as an agent for the chemoprevention of neoplasia.

Animals↗
PubMed1985

Inhibition of carcinogenesis by some minor dietary constituents.

Previous work has shown that food contains a large number of minor dietary constituents that can inhibit the occurrence of cancer. Additional inhibitors from four different natural sources will be the subject of this presentation. 1. Citrus fruit oils. Orange, tangerine, lemon, and grapefruit oils given p.o. induce increased glutathione (GSH) S-transferase activity in tissues of the mouse. When fed in the diet prior to and during the course of administration of benzo(a)pyrene (BP), the four citrus fruit oils inhibit formation of tumors of both the forestomach and lungs of mice. When fed either before or after the administration of 7,12-dimethylbenz(a)anthracene (DMBA) orange oil inhibits mammary tumor formation. 2. Garlic oil. Allyl methyl trisulfide (AMT), a constituent of garlic oil, has been synthesized recently. When given p.o. 96 and 48 hr prior to BP, AMT inhibits the occurrence of forestomach tumors in mice. 3. Green coffee beans. Two diterpene esters, kahweol palmitate and cafestol palmitate, which are potent inducers of GSH S-transferase activity have been isolated from coffee beans. When administered p.o. prior to DMBA the two diterpene esters inhibit mammary tumor formation. 4. Cruciferous vegetables. Several glucosinolates occur in cruciferous vegetables. Efficient procedures for the isolation of these compounds have been developed recently. The inhibitory effects of three of these i.e. glucobrassicin, glucotropaeolin, and glucosinalbin were studied in several animal models. Glucobrassicin caused substantial inhibition of BP-induced neoplasia of the lung and forestomach of the mouse and DMBA-induced neoplasia of the breast in rats. Glucosinalbin and glucotropaeolin are less active in these systems. In addition to protective effects, indoles derived from the hydrolysis of glucobrassicin have potential harmful properties. The implications of multiple properties and factors which may determine their consequence will be discussed.

Animals↗