Non-carcinogenic Polycyclic Hydrocarbons Research Articles

Analysis of technological conditions for the formation and burnout of carcinogenic pahs in boiler flue gases

THE PURPOSE. The necessity of establishing emission standards for highly toxic substances with carcinogenic properties in the context of the implementation of new principles of state regulation of environmental protection activities at energy enterprises is substantiated and confirmed. The analysis of the features of the formation and burnout of carcinogenic polycyclic aromatic hydrocarbons in the flue gases of boilers during the combustion of coals in lowtemperature conditions of the furnace process is carried out. Based on the analysis, the total and partial indicators of the harmfulness of flue gases were calculated in order to assess and predict the overall toxicity of coal combustion products, taking into account the contribution of carcinogenic substances.METHODS. When calculating the overall toxicity of flue gases, a systematic analysis and generalization of experimental data on the content of carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons in the combustion products of low-power boilers was applied.RESULTS. As a result of the performed study, the contribution of carcinogenic and non-carcinogenic polycyclic hydrocarbons to the overall toxicity of boiler flue gases during the combustion of Azeysky, Mugunsky, Cheremkhovsky and Tugnuy coal was determined. It is shown that substances such as benz(a)pyrene, fluoranthene, pyrene and phenanthrene significantly affect the level of the total indicator of the harmfulness of combustion products from 38.8 to 53.6%.CONCLUSION. The obtained research results can be applied at energy enterprises at the stage of substantiating the introduction of regime-technological and environmental measures in order to develop measures to improve environmental efficiency through technological rationing of carcinogenic emissions.

The effects of weak or non-carcinogenic polycyclic hydrocarbons on 7, 12-dimethylbenz[ a]anthracene and benzo[ a]pyrene skin tumor-initiation

Benzo[e]pyrene (B[e]P) inhibited 7,12-dimethylbenz[a]anthracene (DMBA) skin tumor-initiation in mice by 84%, whereas pyrene and fluoranthene inhibited DMBA initiation by 50 and 34%, respectively. However, B[e]P, pyrene and fluoranthene had either no significant effect or a slight enhancing effect on benzo[a]pyrene (B[a]P) skin tumor-initiation. In addition, B[e]P had essentially no effect on the initiating ability of (+/-)B[a]P-7 beta,8 alpha-diol-9 alpha,10 alpha-epoxide. As a tumor-initiator, B[e]P was found to have very weak activity at a 252 microgram/level (0.4 papillomas/mouse at 40 weeks) and no activity at 100 microgram. When given at a dose of 100 microgram twice weekly, B[e]P induced 2.1 papillomas/mouse at 30 weeks, and 25% of the mice had carcinomas at 40 weeks. However, B[e]P carcinogenic activity is weak when compared to B[a]P, which can induce a comparable tumor response at a dose of 5 microgram twice weekly. When B[e]P was tested as a tumor promoter at a dose of 100 microgram twice weekly after DMBA initiation, it induced 4.5 papillomas/mouse at 30 weeks and a 45% carcinoma incidence at 40 weeks, which was approximately twice as effective as B[e]P alone. The data show that B[e]P is a very weak tumor initiator, a weak complete carcinogen, a moderate tumor promoter, possibly a weak co-tumor-initiator when given with B[a]P, and a potent anit-tumor-initiator when given with DMBA. The anti-tumor initiating and co-tumor-initiating effects of B[e]P appear to be related to its ability to modify the conversion of the tumor initiator into an electrophilic intermediate(s) which are capable of covalently binding to DNA. In addition, B[e]P induced epidermal cellular proliferation which may be related to its promoting ability.

Molecular orbital theoretical prediction of the isomeric products formed from reactions of arene oxides and related metabolites of polycyclic aromatic hydrocarbons

MO theoretical calculations based on the perturbational method of Dewar provide good correlation between predicted and observed structures of products formed during: (1) isomerization of arene oxides to phenols; (2) hydration and nucleophilic addition to arene oxides; and (3) dehydration of arene dihydrodiols. The method is equally applicable to the arene oxides, dihydrodiols, etc. derived from carcinogenic and noncarcinogenic polycyclic hydrocarbons. Extension to the related enzymatic reactions occurring during metabolism of carcinogenic hydrocarbons and to the reactions of the biologically active arene diolepoxides and aryloxirenes suggests the potential utility of this approach in predicting (a) metabolite structure and (b) the structural requirements for carcinogenic and mutagenic activity.

Sister Chromatid Exchange and Chromosome Aberration Analysis With the Use of Several Carcinogens and Noncarcinogens: Brief Communication

Several chemical carcinogens and noncarcinogens were tested for their ability to induce sister chromatid exchanges (SCE) and structural chromosome aberrations in cultured V79-4 Chinese hamster cells. All of the direct-acting carcinogens induced a large increase in SCE frequency. Two chemicals, which are mutagenic in microorganisms but whose carcinogenicity is poorly documented, also increased the frequency of SCE. Carcinogenic polycyclic hydrocarbons caused an increased incidence of SCE only when a metabolizing feeder layer was used, whereas no increase was observed with noncarcinogenic polycyclic hydrocarbons. The other noncarcinogens also did not influence the SCE frequency. Although some chemicals increased the frequency of structural chromosome aberrations, no correlation was found between the frequencies of SCE and aberrations.

Activation of carcinogenic polycyclic hydrocarbons in polyoma‐virus‐transformed cells as a prerequisite for polyoma virus induction

Polyoma-virus (PV)-transformed cell clones, which are inducible for virus synthesis by various physical and chemical agents, metabolize the chemically non-reactive carcinogen benzo(a)pyrene (BP) into water soluble products. In cultures of such clones, which metabolize BP to a level of 30-6-% of that of normal cells, up to 10.4% of the cells were induced for PV synthesis by BP, 20-methylcholanthrene (MCA) and 7,12-dimethylbenz(a)anthracene (CMBA). No PV induction was observed with the non-carcinogenic polycyclic hydrocarbons pyrene chrysene and benz(a)-anthracene. A proportion of subclones, isolated from a PV- inducible clone, which metabolized 0.1 mug or less BP per 10-6 cells were all inducible for PV synthesis by these carcinogens. Subclones isolated from an inducible clone pretreated with BP were shown to metabolize less than 0.1 mu BP per 10-6 cells and were resistant to virus induction by the carcinogenic polycyclic hydrocarbons. Benzoflavone, which inhibited the metabolism of BP in clones metabolizing high levels of this carcinogen, also prevented the induction of PV antigen and infectious virus synthesis in these clones. The data indicate a relationship between the carcinogenicity of polycyclic hydrocarbons and their ability to induce virus in the PV-transformed cells and suggest that virus induction depends on metabolic conversion of these hydrocarbons into similar reactive compounds that are responsible for malignant transformation and mutagenesis.

Genetic control of the regulation of cell susceptibility to carcinogenic polycyclic hydrocarbons by cyclic AMP

The metabolism of benzo (a) pyrene (BP) in normal golden hamster and BHK cells in culture was increased by treating the cells with dibutyryl cyclic AMP (dcAMP), prostaglandin E1, theophylline or aminophylline. The largest increase, 6-fold for the normal cells and 20-fold for the BHK cells, was obtained by treatment with both dcAMP and aminophylline. Treatment with aminophylline also stimulated the metabolism of 20-methylcholanthrene and 7,12-dimethylbenz (a) anthracene. The increased metabolism of these three carcinogeneic polycyclic hydrocarbons was associated with an increased cytotoxicity. Treatment with aminophylline increased the cytotoxicity of five other potent and weak carcinogenic polycyclic hydrocarbons, but not of two non-carcinogenic polycyclic hydrocarbons. The amount of BP metabolism in 27 different cell types from various mammals, including humans, ranged from less than 0.1 mug to 2.3 mug metabolized BP per 10-6 cells. Treatment of these different cell types with aminophylline gave either an increase in BP metabolism, an induction of metabolism in cells that did not metabolize without aminophylline, or no induction after treatment with aminophylline and dcAMP. The existence of responding and non-responding cell lines indicates that the regulation of the level of polycyclic hydrocarbon metabolism by dcAMP is genetically controlled. The induction of metabolism in cells that did not metabolize without aminophylline resulted in the conversion of cell resistance to cell susceptibility to the cytotoxic effect of BP. Treatment with dcAMP and aminophylline can therefore be used to increase the sensitivity of screening tests for chemical carcinogens.

The adenyl cyclase system and carcinogenesis: Decreased responsiveness of mouse epidermis to isoproterenol after 3,4-benzpyrene treatment

The concentration of cyclic AMP in untreated and acetone-treated mouse epidermis was increased 9–11 fold 10 min. after the intraperitoneal injection of L-isoproterenol. The response to isoproterenol was unaffected 30 min. after a single application of 3,4-benzpyrene in acetone, but was reduced to a 2.7 fold increase when tested after 24 hours. The increase in epidermal cyclic AMP following isoproterenol injection varied between 2.1 and 2.5 fold with repeated applications of 3,4-benzpyrene over periods of up to 55 days. The response to isoproterenol was unaffected by 1,2-benzpyrene, a non-carcinogenic polycyclic hydrocarbon.

Proton magnetic resonance coupling constants and π-bond orders in the active regions of carcinogenic and non-carcinogenic polycyclic hydrocarbons

Proton magnetic resonance (PMR) spin-spin coupling constants ( J) depend on the geometry and electronic configuration of the molecule and on its interactions with other molecules. Empirically, ortho coupling constants, J NN′ ortho , in polycyclic hydrocarbons of varying carcinogenicity appear to be related linearly to Hückel molecular-orbital (HMO) π-bond orders, P NN′ , as are the corresponding bond lengths, R NN′ . We find a lack of correlation between J NN′ ortho and carcinogenicity indices; thus there is a relatively large difference in J NN′ ortho for the K region of benz[ a]pyrene and 7,12-dimethylbenz[ a]anthracene, which are both highly active.

Chemical linkage of carcinogenic 3,4-benzpyrene to DNA in aqueous solution induced by peroxide and iodine.

THE origin of the biological specificity of polycyclic hydrocarbons has long confronted investigators interested in carcinogenesis. The affinity and the extent of physical binding of carcinogenic and non-carcinogenic polycyclic hydrocarbons (for example, 3,4-benzpyrene against 1,2-benzpyrene or 1,2,5,6-dibenzanthracene against 1,2,3,4-dibenzanthracene) to DNA cannot be correlated with carcinogenicity1. Chemical complexes of polycyclic carcinogens with DNA have been found in biological systems2,3, and the available data indicate that the extent of complex formation may be correlated with the carcinogenic potency of these compounds3. Ts'o and Lu4 have reported the formation of a covalent linkage between 3,4-benzpyrene (3,4-BP) and DNA in aqueous solution, induced by photoirradiation. Preliminary experiments with carcinogenic and non-carcinogenic hydrocarbons have shown no selective activation of carcinogenic compounds by photoirradiation. Rapaport and Ts'o5 have achieved a covalent linkage between 3,4-BP and DNA by X-irradiation which suggests that polycyclic hydrocarbons may be activated by hydroxyl radicals. Rochlitz6 reported that a covalent linkage between 3,4-BP and pyridine had been induced by iodine vapour in a pyridine–solid phase system. Here we wish to report the formation of a 3,4-BP–DNA covalent linkage in an aqueous, neutral solution, at 0°–50° C, induced by peroxide and iodine. Little or no 1,2-BP–DNA chemical complex formation was found in identical conditions. Thus the chemical reactivity of this pair of isomers with DNA in the present aqueous system can be correlated with their carcinogenicity.

The stimulation of hydroxylation by carcinogenic and non-carcinogenic compounds

Pretreatment of young rats and mice with certain drugs and polycyclic hydrocarbons stimulates the hydroxylation of biphenyl by liver microsomal preparations. Phenobarbitone, nikethamide and meprobamate, all increase the 4-hydroxylation of biphenyl but have little effect on the 2-hydroxylation. In contrast, the carcinogenic polycyclic hydrocarbons, 3,4-benzpyrene, 20-methylcholanthrene, and 1, 2, 5, 6-dibenzanthracene preferentially stimulate the 2-hydroxylation of biphenyl. Non-carcinogenic polycyclic hydrocarbons such as 1, 2, 6, 7-dibenzpyrene and 2, 3, 6, 7-dibenzanthracene stimulate neither mode of hydroxylation. Biphenyl is metabolized in vivo into 4-hydroxybiphenyl (20 per cent of the dose in rats, 25 per cent in mice) and 2-hydroxybiphenyl (2 per cent in rats, 5.5 per cent in mice). Pretreatment with phenobarbitone produces moderate stimulation of the 4-hydroxylation in rats, but not mice: 2-hydroxylation is unaffected. Pretreatment with benzpyrene produces stimulation of 2-hydroxylation in both species, but does not affect the 4-hydroxylation. It is suggested that a correlation may exist between the carcinogenicity of polycyclic hydrocarbons and their induction of the hepatic microsomal enzyme responsible for the 2-hydroxylation of biphenyl.

EFFECTS OF POLYCYCLIC AROMATIC CARCINOGENS ON VIRAL REPLICATION: SIMILARITY TO ACTINOMYCIN D.

When incorporated into a nutrient overlay, the carcinogenic hydrocarbons benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene inhibit plaque formation by herpes virus and vaccinia virus, DNA viruses, but not by Sindbis virus, an RNA virus. These carcinogens also decrease herpes and vaccinia virus yields in liquid medium, without affecting Sindbis virus yields. Four structurally related, but noncarcinogenic polycyclic hydrocarbons, namely benzo[e]pyrene, pyrene, benz[a]anthracene and anthracene, have no inhibitory effect on DNA virus replication. Taken together with the known inhibition of interferon production, these effects on virus growth resemble the action of actinomycin D and hence provide evidence for a selective interaction of these carcinogens with DNA.

Use of sebaceous-gland test of primary cigarette-tar fractions and of certain noncarcinogenic polycyclic hydrocarbons.

CancerVolume 10, Issue 2 p. 250-254 ArticleFree Access Use of sebaceous-gland test of primary cigarette-tar fractions and of certain noncarcinogenic polycyclic hydrocarbons V. Suntzeff M.D., V. Suntzeff M.D. Wernse Cancer Research Laboratory and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Section of Epidemiology, Sloan-Kettering Institute for Cancer Research, Memorial Center for Cancer and Allied Diseases, New York, New YorkSearch for more papers by this authorA. B. Croninger M.A., A. B. Croninger M.A. Wernse Cancer Research Laboratory and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Section of Epidemiology, Sloan-Kettering Institute for Cancer Research, Memorial Center for Cancer and Allied Diseases, New York, New YorkSearch for more papers by this authorE. L. Wynder M.D., E. L. Wynder M.D. Wernse Cancer Research Laboratory and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Section of Epidemiology, Sloan-Kettering Institute for Cancer Research, Memorial Center for Cancer and Allied Diseases, New York, New YorkSearch for more papers by this authorE. V. Cowdry PH.D., E. V. Cowdry PH.D. Wernse Cancer Research Laboratory and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Section of Epidemiology, Sloan-Kettering Institute for Cancer Research, Memorial Center for Cancer and Allied Diseases, New York, New YorkSearch for more papers by this authorE. A. Graham M.D., E. A. Graham M.D. Wernse Cancer Research Laboratory and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Section of Epidemiology, Sloan-Kettering Institute for Cancer Research, Memorial Center for Cancer and Allied Diseases, New York, New York Deceased March 4, 1957Search for more papers by this author V. Suntzeff M.D., V. Suntzeff M.D. Wernse Cancer Research Laboratory and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Section of Epidemiology, Sloan-Kettering Institute for Cancer Research, Memorial Center for Cancer and Allied Diseases, New York, New YorkSearch for more papers by this authorA. B. Croninger M.A., A. B. Croninger M.A. Wernse Cancer Research Laboratory and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Section of Epidemiology, Sloan-Kettering Institute for Cancer Research, Memorial Center for Cancer and Allied Diseases, New York, New YorkSearch for more papers by this authorE. L. Wynder M.D., E. L. Wynder M.D. Wernse Cancer Research Laboratory and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Section of Epidemiology, Sloan-Kettering Institute for Cancer Research, Memorial Center for Cancer and Allied Diseases, New York, New YorkSearch for more papers by this authorE. V. Cowdry PH.D., E. V. Cowdry PH.D. Wernse Cancer Research Laboratory and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Section of Epidemiology, Sloan-Kettering Institute for Cancer Research, Memorial Center for Cancer and Allied Diseases, New York, New YorkSearch for more papers by this authorE. A. Graham M.D., E. A. Graham M.D. Wernse Cancer Research Laboratory and the Department of Surgery, Washington University School of Medicine, St. Louis, Missouri Section of Epidemiology, Sloan-Kettering Institute for Cancer Research, Memorial Center for Cancer and Allied Diseases, New York, New York Deceased March 4, 1957Search for more papers by this author First published: March/April 1957 https://doi.org/10.1002/1097-0142(195703/04)10:2<250::AID-CNCR2820100207>3.0.CO;2-ZCitations: 16 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume10, Issue2March/April 1957Pages 250-254 ReferencesRelatedInformation