Search PubMed⌕ Search

Biomedical subjects

W Lijinsky

Publications and source records attributed to W Lijinsky.

303 records · Page 17Linked to original sources
PubMedDate not supplied

The formation and occurrence of polynuclear aromatic hydrocarbons associated with food.

Polynuclear aromatic hydrocarbons are common contaminants of processed food, usually at trace levels. These hydrocarbons are products of combustion and pyrolysis, and are present in petroleum and coal, and in products derived from them. Most polynuclear aromatic hydrocarbons are not carcinogenic, but some of them are, and a few are potent inducers of skin and lung tumors in mice. Their carcinogenic properties have not been fully explored, but they seem to be less potent by ingestion or inhalation, and they are known as a group to produce cancer in humans. The most effective carcinogens among them are those with 5 or 6 fused rings, and these tend to be less prevalent in mixtures than the 3- and 4-ring hydrocarbons, most of which are not carcinogenic. Sophisticated analytical methods, using solvent extraction and chromatography have been developed to detect and measure polynuclear aromatic hydrocarbons at levels of 1 in 10(9) (1 part per billion) or less, and these have been applied to the measurement of individual compounds in foods, as well as in products of combustion and pyrolysis. Wood smoke and smoked foods contain the carcinogenic benzo[a]pyrene at levels of 1 ppb, and other hydrocarbons; liquid smoke has lower levels. Crude vegetable oils have higher concentrations, but purified 'deodorized' oils have benzo[a]pyrene levels near 1 ppb. Sausages cooked over burning logs had as much as 200 ppb benzo[a]pyrene. Charcoal-broiled steaks and ground meat had benzo[a]pyrene concentrations up to 50 micrograms/kg, while less fatty pork and chicken had lower concentrations (up to 10 micrograms/kg). It was probable that the rendered fat dripped on to the hot charcoal and pyrolyzed to form quantities of polynuclear aromatic hydrocarbons, which rose with the smoke to deposit on the meat. Therefore, oven cooking or cooking with a heat source above the meat, or segregation of the meat from the smoke resulted in food containing negligible amounts of polynuclear aromatic hydrocarbons. Modifications of cookings practices accordingly would greatly reduce exposure to this group of carcinogens.

Animals↗
PubMedDate not supplied

Carcinogenesis by nitrosobis-(2-oxopropyl)amine labeled with deuterium and by nitroso-2-hydroxypropyl-2-oxopropylamine in rats and hamsters.

The effects of the labeling with deuterium of the alpha-methylene groups of the carcinogen nitrosobis-(2-oxopropyl)amine (NBOP) on its carcinogenic effectiveness in rats and hamsters have been studied. The greater strength of the C-D bond compared with the C-H bond often leads to slower metabolism and lesser carcinogenic activity. When NBOP and NBOP-d4 were given to male and female rats in drinking water at equimolar doses, the mortality rate from tumors was lower in the rats given the deuterium-labeled compound, although the results were statistically significant (P = 0.012) only in males. The incidences of tumors of several groups was similar for NBOP and NBOP-d4, but there was a marked difference between males and females, females having a high incidence of liver tumors, and males very few. When NBOP and NBOP-d4 were given by gavage to rats or Syrian hamsters at identical doses there was no difference in rate of mortality from tumors, or in the pattern of tumors induced by either compound. In rats, both compounds were given at two dose rates, and in neither was a difference seen. To complement the studies with NBOP, a normal reduction product formed metabolically in vivo, nitroso-(2-hydroxypropyl) (2-oxopropyl)amine (NHPOP) was administered to rats in drinking water at the same dose rate. In male rats, the mortality rate was lower with NHPOP than with NBOP, while with female rats the opposite was the case (P less than 0.01 in both cases) and there was little difference in the pattern of tumors induced in either sex. NHPOP appears to have a quite distinct carcinogenic effect from NBOP, suggesting that the metabolic conversion of one to the other does not play a large role. The weak deuterium-isotope effect of NBOP-d4 given to rats in drinking water, but not detected in rats or hamsters treated by gavage, suggests that alpha-oxidation of NBOP is not likely to be a rate-limiting step in carcinogenesis by NBOP.

Animals↗
PubMedDate not supplied

Thermospray liquid chromatography/mass spectrometry studies on mechanisms of nucleic acid alkylation by some deuterated carcinogens.

Alkylation of liver nucleic acids of rats treated with nitrosobis(2-oxopropyl)amine (BOP), nitrosomethyl(2-oxopropyl)amine (NMOP), and (methylazoxy)methane (AOM) was studied by using deuterium-labeled compounds. Six hours after treatment of each rat with 5-10 mg of compound, nucleic acids were isolated from the liver of two rats and hydrolyzed in dilute acid, and the fraction containing 7-methylguanine (7-MeG) was separated by ion-exchange high-pressure liquid chromatography. After purification by repeated chromatography, the sample was analyzed by liquid chromatography in ammonium acetate coupled with thermospray positive ion mass spectrometry. AOM containing a deuterated methyl group proximal to the oxygen-bearing nitrogen gave 7-MeG containing three deuterium atoms (169 amu), whereas AOM having the methyl group distal to oxygen deuterated produced 7-MeG without deuterium (166 amu). This indicates that methylation of nucleic acids is through oxidation of AOM to (methylazoxy)methanol and the corresponding aldehyde. BOP-d4, in which both alpha-methylenes contained deuterium, gave rise to 7-MeG containing two atoms of deuterium (168 amu). NMOP-d5, with deuterium in the N-methyl and in the alpha-methylene, gave rise only to 7-MeG containing three deuterium atoms. The methyl-d3 group must originate from the N-methyl of NMOP, probably through formation of a methyldiazonium ion. This result lends support to a mechanism involving a Baeyer-Villiger oxidation of the ketone, rather than oxidation of the N-methyl and formation of an (oxopropyl)diazonium ion, which could give rise to a methylating agent following cyclization.

Alkylation↗
PubMedDate not supplied

Failure of methapyrilene to induce tumors in hamsters or guinea pigs.

In a small-scale experiment, 12 male and 12 female strain 2 guinea pigs were treated by gavage twice a week for 78 wk with a 200-mg/kg body weight dose of methapyrilene hydrochloride dissolved in water, a total dose of approximately 30 g/kg body weight. By the end of the treatment more than half of the animals were still alive: survivors were killed at 132 wk. A group of 20 male Syrian golden hamsters was treated twice a week by gavage with 15 mg methapyrilene hydrochloride for 58 wk, a total dose of approximately 15 g/kg body weight. Thirteen animals survived an acute convulsant effect, and the last 4 were killed at wk 61. There was no significant incidence of any tumor that could be attributed to the treatment in either guinea pigs or hamsters.

Aminopyridines↗
PubMedDate not supplied

A study of the carcinogenicity of glycidol in Syrian hamsters.

The industrial chemical glycidol is a directly acting mutagen and a broadly acting carcinogen in rats. It was administered to Syrian golden hamsters (20 male and 20 female) by gavage of 12 mg twice a week for 60 weeks. The total dose per animal was 1.45 g or 20 mmol. Survival was not different from control hamsters treated with corn oil/ethyl acetate. Of the treated males, 9 had tumors and 13 of the treated females had tumors, some of which were adrenal cortex tumors seen in controls. More tumors were seen in the glycidol-treated hamsters than in controls, but the spleen was the only notable target organ and the number of animals with spleen hemangiosarcomas was small. Glycidol appeared to be less carcinogenic in hamsters than in rats or mice.

1-Propanol↗
PubMedDate not supplied

Carcinogenesis in rats by substituted dialkylnitrosamines given by gavage.

A number of nitrosamines that have been studied by administration to rats as solutions in drinking water have been examined by gavage administration of similar doses, for assessment of the role of pharmacokinetics in organ-specific carcinogenesis. Methylnitrosoethylamine was more effective as a liver carcinogen by gavage than in drinking water and gave rise to tumors of the lung and nasal mucosa by the former route, but not the latter. By gavage, methylnitroso-2-oxopropylamine and methylnitroso-2-hydroxypropylamine induced mainly tumors of the esophagus, as they did when given to rats in drinking water, but the potency was greater by gavage. At a higher dose rate (85 micromoles per week) methylnitrosohydroxypropylamine induced a high incidence of mesenchymal tumors of the kidney and lung tumors, in addition to esophageal tumors, but methylnitrosooxopropylamine did not. The tobacco-specific carcinogen NNK induced tumors of the liver, and to a lesser extent, of the lung and nasal mucosa when given by gavage to rats, as it did by other routes of administration. The similarly basic nitrosamine methylnitroso-N, N-dimethylaminoethylamine was equally potent, whether administered by gavage or in drinking water to rats, and gave rise only to tumors of the esophagus. The cyclic nitrosamine nitrosomorpholine was equally effective by gavage and in drinking water, but induced in rats more esophageal tumors by gavage in addition to a high incidence of liver tumors. Its 2-hydroxy derivative, a postulated metabolic intermediate of nitrosodiethanolamine, was a very much weaker carcinogen than either the latter or nitrosomorpholine, and induced low incidences of liver and lung tumors toward the end of the lifespan of the rats.

Administration, Oral↗
PubMedDate not supplied

Carcinogenesis in rats by nitrosodialkylureas containing oxygenated alkyl groups.

A number of asymmetric nitrosodialkylureas containing ethyl, hydroxyethyl, 2-hydroxypropyl, 2-oxopropyl or chloroethyl on one or the other side of the nitroso function were given to male and female F344 rats in drinking water. The two compounds containing a 2-oxopropyl group, ethylnitrosooxopropylurea and oxopropylnitrosochloroethylurea were also given by gavage at the same weekly doses as in drinking water. The effect was greater following gavage treatment, both in tumor incidence and in mortality rate. The most potent carcinogen was ethylnitrosooxopropylurea which induced a large variety of tumors, including lung, nervous system, colon, intestine, thyroid, skin and uterus tumors, mammary adenocarcinomas and mesotheliomas. A similar pattern of tumors was induced by ethylnitrosohydroxyethylurea and hydroxyethylnitrosoethylurea. Hydroxyethylnitrosochloroethylurea, hydroxypropylnitrosochloroethylurea and oxopropylnitrosochloroethylurea gave rise to tumors in fewer organs. Chloroethylnitrosohydroxypropylurea was very toxic to the kidneys and induced a few lung tumors. Skin tumors were commonly induced by the nitrosodialkylureas in drinking water, but not when given by gavage.

Administration, Oral↗
PubMedDate not supplied

Thymic T-cell lymphoma with the CD8+ (OX-8), CD4+ (W3/25) phenotype, induced in F344/NCr rats by nitroso-2-hydroxypropylurea.

Thymic T-cell lymphomas were induced by administration of nitroso-2-hydroxypropylurea (NHPU) at a dose of 1.6 mg by gavage twice weekly for each of 20 weeks in F344/NCr rats. Lymphomas began to appear 5-10 weeks after the first intubation. Primary and transplantable tumors were subjected to morphological, histogenetic and immunological characterization. Lymphomas composed of medium-sized lymphocytes (prolymphocytes) arose within individual thymic lobules, often in atrophic thymic lobes and metastasized slowly to the T-cell zones of the splenic white pulp. The tissue fixative was important for tumor morphology and classification, with Bouin's fluid markedly superior to formalin. Transplantable tumors were similar morphologically except for one lymphoblastic lymphoma, but all transplants metastasized quickly to spleen, liver, thymus, and other tissues. Fluorescence-activated cell sorter (FACS) analysis of primary and transplantable lymphomas revealed cells of the T-cell lineage, with tumor cells expressing both OX-8 (CD8) and W3/25 (CD4) antigens. Immunoperoxidase studies of spleen showed infiltration of OX-8+ tumor cells first into T-cell dependent areas of the splenic white pulp.

Animals↗
PubMedDate not supplied

Carcinogenicity and mutagenicity of N-nitroso compounds.

The carcinogenic activities in rats and hamsters and the mutagenic activity in Salmonella of a number of N-nitroso compounds belonging to various classes have been compared. While most directly acting N-nitroso compounds and those requiring metabolic activation are mutagenic with appropriate activation and seem to alkylate DNA in vivo, there are exceptions. Some of these are mutagens that are not carcinogenic; others are carcinogens that are nonmutagenic. Even among the mutagenic carcinogens, there is no quantitative relationship between mutagenic and carcinogenic activities. This implies to directly acting compounds and to those requiring metabolic activation. The lack of congruence between the two activities among the nitrosamines is due to the complexity of the metabolic activating processes leading to formation of proximate carcinogens. The deficiencies in the mutagenesis assay appear to arise from a lack of the necessary enzymes in the liver microsomal fractions used for activation. Nitrosamines bearing oxygen on the beta carbon of an alkyl chain are not oxidized by rat microsomal enzymes and hence are not converted to bacterial mutagens by rat liver microsomes. Bacterial mutagenicity is not a guide to carcinogenic activity of N-nitroso compounds or to the mechanisms by which these compounds induce cancer.

Animals↗
PubMedDate not supplied

Species differences in carcinogenesis.

There are differences in response of different species to many carcinogens. Different organs respond to particular carcinogens, there are differences in potency (including resistance of some species), and there are varying effects of other parameters. Although animal studies identify carcinogens, it is impossible to predict accurately the potency or the target organ in humans of any carcinogen. Inter-species differences in response to carcinogens can be due to differences in metabolism and activation. However, even in the case of directly acting carcinogens, such as alkylnitrosoureas, quantitative differences in alkylation of DNA are insufficient to explain the differences in response of particular organs. Yet unknown reactions or interactions of carcinogens must be key factors in inter-species differences.

Alkylation↗