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Biomedical subjects

L W Wattenberg

Publications and source records attributed to L W Wattenberg.

At least 73 records · Page 4Linked to original sources
PubMed1979

Inhibitory effects of butylated hydroxyanisole on methylazoxymethanol acetate-induced neoplasia of the large intestine and on nicotinamide adenine dinucleotide-dependent alcohol dehydrogenase activity in mice.

Butylated hydroxyanisole (BHA), a widely used food additive, previously was found to inhibit various chemical carcinogens. In the present work, BHA, when added to the diet, inhibited the carcinogenic action of methylazoxymethanol (MAM) acetate on the large intestine of female CF1 mice. The effects of BHA on nicotinamide adenine dinucleotide (NAD+)-dependent alcohol dehydrogenase, a postulated activating enzyme for MAM, were determined. BHA reduced this enzyme activity in vitro in crude tissue preparations of large intestine and liver. The parallel finding of BHA inhibition of MAM acetate carcinogenesis of the large bowel and of NAD'-dependent dehydrogenase activity lends support to the postulated role of the dehydrogenase activity in activating MAM to an ultimate carcinogenic form. However, BHA has multiple biologic actions so that its inhibitory effect on MAM acetate-induced neoplasia of the large intestine may entail some other mechanism.

Alcohol Oxidoreductases↗
PubMed1979

Neoplastic effects of oral administration of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and their inhibition by butylated hydroxyanisole.

The neoplastic effects of administration of benzo[a]pyrene (BP) and (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP 7,8-dihydrodiol) by oral intubation to noninbred female Ha:ICR mice have been determined. Under the experimental conditions, BP induced papillomas of the forestomach. BP 7,8-dihydrodiol also induced papillomas of the forestomach and was more potent than BP. In addition, administration of BP 7,8-dihydrodiol caused a large number of pulmonary adenomas and lymphomas. Butylated hydroxyanisole (BHA) added to the diet at a concentration of 5 mg/g inhibited BP-induced neoplasia of the forestomach. BHA also inhibited neoplasia of the forestomach, lungs, and lymphoid tissues that was caused by administration of BP 7,8-dihydrodiol. These data suggest that the inhibitory effect of BHA on BP carcinogenesis may entail events that occur subsequent to the formation of BP 7,8-dihydrodiol.

Adenoma↗
PubMed1978

Effects of administration to mice of butylated hydroxyanisole by oral intubation on benzo[a]pyrene-induced pulmonary adenoma formation and metabolism of benzo[a]pyrene.

Administration of butylated hydroxyanisole (BHA) by oral intubation 4 hours before challenge with benzo[a]pyrene (BP) inhibited the formation of pulmonary adenomas in A/HeJ mice. Incubation of BP with liver microsomes from mice that received BHA 2,4, or 8 hours before being killed resulted in less binding of BP metabolites to added DNA than occurred with control microsomes. High-pressure liquid chromatography studies of the BP metabolite pattern produced by the incubation of BP with liver microsomes from mice given BHA by oral intubation showed a decrease in formation of BP-4,5-oxide and 9-hydroxybenzo[a]pyrene. In contrast, the formation of 3-hydroxybenzo[a]-pyrene was increased. The was increased. The short interval between the administration of BHA by oral intubation and the observed biochemical changes indicated that BHA could exert a direct effect on the microsomal metabolism of BP. These changes in metabolism of BP occurred under conditions of BHA administration that produced a decreased neoplastic response to this carcinogen.

Adenoma↗
PubMed1978

Inhibition of 1,2-dimethylhydrazine-induced neoplasia of the large intestine in female CF1 mice by carbon disulfide.

Disulfiram, diethyldithiocarbamate, and bis-(ethylxanthogen) inhibit symmetrical 1,2-dimethylhydrazine dihydrochloride (DMH)-induced neoplasia of the large bowel in female CF1 mice. These three compounds contain a carbon disulfide (CS2) moiety in their structure. In the present study, CS2 itself was found to inhibit DMH-induced neoplasia of the large bowel in female CF1 mice. Thus a relatively simple compound is now available for investigation of the mechanism of inhibition of DMH-induced neoplasia by a group of sulfur-containing inhibitors having common structural features.

Adenocarcinoma↗
PubMed1978

Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles.

Indole-3-carbinol, 3,3'-diindolylmethane, and indole-3-acetonitrile, three indoles occurring in edible cruciferous vegetables, have been studied for their effects on 7,12-dimethylbenz(a)anthracene-induced mammary tumor formation in female Sprague-Dawley rats and on benzo(a)pyrene-induced neoplasia of the forestomach in female ICR/Ha mice. When given by p.o. intubation 20 hr prior to 7,12-dimethylbenz(a)anthracene administration, indole-3-carbinol and 3,3'-diindolylmethane had an inhibitory effect on mammary tumor formation, but indole-3-acetonitrile was inactive. Indole-3-carbinol when added to the diet for 8 days prior to challenge with 7,12-dimethylbenz(a)anthracene inhibited mammary tumor formation, whereas indole-3-acetonitrile did not. Dietary administration of all three indoles inhibited benzo(a)pyrene-induced neoplasia of the forestomach in ICR/Ha mice. The identification of dietary constituents that can inhibit chemical carcinogens ultimately may be of value in understanding the balance of factors that determines the neoplastic response to these cancer-producing agents in the environment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Inhibits of of colon carcinogenesis.

Disulfiram (tetraethylthiuram disulfide, Antabuse) and sodium diethyldithiocarbamate, when added to the diet, inhibit 1,2-dimethylhydrazine (DMH)-induced neoplasia of the large bowel in female CF1 mice. Ethylene bis(dithiocarbamato)manganese (Maneb) and bis(ethylxanthogen), two pesticides with structural similarities to disulfiram, produce comparable inhibition of DHM. In other work, disulfiram was found to inhibit the carcinogenic effect of azoxymethane (AOM) on the large bowel. Under comparable conditions the inhibition of AOM was considerably less than that obtained with DMH as the carcinogen. The data suggest that disulfiram inhibits DMH metabolism at more than one oxidative step.

Animals↗
PubMed1977

Inhibition of carcinogenic effects of polycyclic hydrocarbons by benzyl isothiocyanate and related compounds.

Benzyl isothiocyanate and phenethyl isothiocyanate, two compounds found in cruciferous plants, and phenyl isothiocyanate, a synthetic compound, all inhibit 7,12-dimethylbenz[a]anthracene (CMBA)-induced mammary tumor formation in female Sprague-Dawley rats when administered 4 hours prior to the DMBA. Comparable studies in which benzyl isothiocyanate was administered 24 hours before or 4 hours after DMBA showed almost complete loss of inhibition. Additions of benzyl isothiocyanate or phenethyl isothiocyanate to a diet containing CMBA inhibited formation of neoplasms of the forestomach and pulmonary adenomas in female ICR/Ha mice. Addition of benzyl isothiocyanate to a diet containing benzo[a]pyrene also inhibited carcinogenesis of the mouse forestomach due to this carcinogen. The finding of two additional anutrient dietary compounds which inhibit chemical carcinogenesis focuses on the possibility that dietary constituents of this nature may diminish the impact of exposures to chemical carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Effects of butylated hydroxyanisole on the metabolism of benzo[a]pyrene by mouse liver microsomes.

The metabolites of tritium-labeled benzo[a[pyrene (BP) extracted from liver microsomes prepared by butylated hydroxyanisole (BHA)-fed and control female A/HeJ mice were analyzed by high-pressure liquid chromatography. There was an overall decrease in diol formation as well as an increase in the phenol formation in microsomal incubations from the BHA-fed mice compared to the controls. The dione region, when analyzed together with the BP-4,5-oxide peak, showed an overall decrease with BHA feeding. The BP-4,5-oxide was isolated and identified. It was present in both the BHA-fed and control microsomal incubations but was substantially reduced in the former. BP-9,10-oxide and BP-7,8-oxide were not directly demonstrated. Data based on summation of diols and phenols resulting from the breakdown of these oxides indicated that they were present in reduced amounts in the microsomal incubation from BHA-fed mice. The 3-hydroxybenzo[a]pyrene (3-HOBP) was the major metabolite in both microsomal incubations and was present in a significantly higher percentage in the incubations from the BHA-fed mice when compared to control mice. Thus BHA resulted in two metabolic alterations which could result in its exerting an inhibitory effect on BP-induced carcinogenesis. The first was an increase in 3-HOBP, a metabolite of detoxification, and the second was a decrease in epoxidation, which is an activation process.

Animals↗
PubMed1976

Dietary constituents altering the responses to chemical carcinogens.

This paper deals with two categories of compounds having the capacity to inhibit the neoplastic effects of chemical carcinogens on the host. The first are inducers of increased microsomal mixed function oxidase activity. An increasing number of these inducers are being found in natural products. Cruciferous vegetables including brussels sprouts, cabbage, and cauliflower contain such compounds. Recently indole-3-acetonitrile, indole-3-carbinol and 3,3'-diindolylmethane have been identified as inducers in these three plants. Other naturally occurring inducers include flavones, safrole, isosafrole, beta-ionone, and oxidized sterols. Since previous work has shown that synthetic inducers may protect against chemical carcinogens, the composition of the diet could play a role in inhibiting the neoplastic response to these carcinogenic agents. The second category of inhibitors comprises the antioxidants. Several of these compounds have been found to inhibit the carcinogenic effects of a variety of chemical carcinogens. Considerable work of this nature has been done with butylated hydroxyanisole and butylated hydroxytoluene two antioxidants extensively used as food additives. Other antioxidants having carcinogen inhibiting capacities include ethoxyquin, disulfiram, and dimethyldithiocarbamate.

Animals↗
PubMed1976

Inhibition of macromolecular binding of benzo(a)pyrene and inhibition of neoplasia by disulfiram in the mouse forestomach.

Benzo[a]pyrene (BP) administered to female outbred ICR/Ha mice by oral intubation induced neoplasia in the forestomach after 30 weeks in more than 90% of treated animals. However, no tumors occurred at that site if 1% disulfiram was added to the experimental diet. This inhibition of tumor formation was paralleled by a large inhibition of macromolecular binding of [3H]BP and [14C]BP to RNA and protein in the forestomach. The inhibitory effect of specific binding was strongest in the RNA fraction isolated at 8,000 X g for 20 minutes (6 times that of the control) and weakest in the DNA fraction (no significant difference). The highest specific binding was measured in the RNA fraction isolated at 32,000 X g for 120 minutes and the lowest binding in the DNA fraction. The relative distribution of the BP binding was such that greater than 90% of the BP was bound to protein and less than 1% was bound to DNA. Of the total inhibition of BP binding to all the macromolecular species studied, that to protein constituted the largest component (95%). In contrast to the forestomach, no inhibitory effect of BP binding to DNA, RNA, or protein by disulfiram was found in the liver, which remained free of cancer under the experimental conditions employed.

Animals↗
PubMed1976

Stimulatory effect of vegetables on intestinal drug metabolism in the rat.

The intestinal metabolism of hexobarbital, phenacetin, 7-ethoxycoumarin and benzo [a] pyrene in vitro was increased in rats fed either dried Brussels sprouts or dried cabbage in a nutritionally complete semisynthetic diet as compared to rats fed only the semisynthetic diet. Pretreatment of rats with several indoles present in Brussels sprouts and cabbage also stimulated intestinal drug metabolism, but the effect was smaller than when dried Brussels sprouts or dried cabbage was fed. The results obtained suggest a need for studies in man to determine whether vegetables and other dietary constituents can stimulate the intestinal metabolism of drugs and thereby alter their biological effects.

Animals↗
PubMed1975

Effects of dietary constituents on the metabolism of chemical carcinogens.

Dietary constituents of 2 types have been shown to affect the metabolism of chemical carcinogens by the microsomal mixed-function oxidase system. Naturally occurring inducers of increased activity of this system are present in plants. Cruciferous vegetables including Brussels sprouts, cabbage, and cauliflower are relatively potent in this regard. From these vegetables, three indoles with inducing activity have been identified. These are indole-3-acetonitrile, indole-3-carbinol, and 3,3'-diindolylmethane. A 2nd type of dietary constituent affecting the microsomal mixed-function oxidase system is added phenolic antioxidant, i.e., butylated hydroxyanisole (BHA) and butylated hydroxytoluene. Studies of the effect of BHA on metabolism of bezo(a)-pyrene by liver microsomes have been carried out. BHA feeding results in microsomal changes. The cytochrome P-450 shows altered spectral characteristics, and the aryl hydrocarbon hydroxylase system of these microsomes has an increased sensitivity to inhibition by alpha-naphthoflavone. In addition, there is a decrease in binding of metabolites of benzo(a)pyrene to DNA upon incubation of these microsomes of induction of increased mixed function oxidase activity have shown that increased levels of activity protect against administration of chemical carcinogens. BHA and butylated hydroxytoluene also have been found to exert a protective effect against chemical carcinogens. Thus the constituents of the diet could be of consequence in the neoplastic response to exposure to carcinogens in the environment.

Animals↗