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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Narrow temperature range distillates from biologically active solvent refined coal-I and -II heavy-end coal liquids were fractionated according to chemical class and assayed for initiation of skin carcinogenesis in CD-1 mice. In addition, instrumental chemical analyses were performed on the distillates and their chemical fractions. Results showed that initiation activity in these complex fuel mixtures could be segregated both by boiling point and chemical class. Neutral polycyclic aromatic hydrocarbon fractions were the most active of the chemical classes, with some initiating activity being shown by nitrogen-containing polycyclic aromatic hydrocarbon. Aliphatic and hydroxylated polycyclic aromatic hydrocarbon fractions showed little or no initiating activity. For the two solvent refined coal-II distillates studied, initiating activity was substantially higher in the material boiling above 850 degrees F than in that boiling 800-850 degrees F, although both contained essentially the same concentrations of benzo[a]pyrene. These data indicate that the overall initiating activity of these complex mixtures is highly dependent on interactions of the many chemical carcinogens and that relative concentrations of known carcinogenic polycyclic aromatic hydrocarbons, such as benzo[a]pyrene and dimethylbenz[a]anthracene, are not the sole determinants of initiating activity.
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PMID:Fractionation of skin tumor-initiating activity in coal liquids. 648 77

Nitrogen mustard and nor-nitrogen mustard were investigated in Salmonella typhimurium and human lymphocytes for genotoxicity. Point mutations were assessed using the plate test, the conventional spot test and a method in which the substances were not in direct contact with the microorganisms. Both compounds were active, but nor-nitrogen mustard was far more potent than nitrogen mustard in all bacterial systems. Cytogenetic experiments with human lymphocytes revealed that both compounds induced a dose dependent increase in chromosomal aberrations and sister chromatid exchanges, but that nitrogen mustard was 10 times more potent than nor-nitrogen mustard. Thus, the spectrum of activity for nor-nitrogen mustard and nitrogen mustard differ. Nor-nitrogen mustard was more effective in inducing point mutation damage than nitrogen mustard and a reversal of potency was found for cytogenetic damage. These results indicate that although these two substances induce the same type of DNA lesions the amounts of the different DNA adducts vary.
Carcinogenesis 1984 Dec
PMID:Comparative genotoxicity of nitrogen mustard and nor-nitrogen mustard. 649 15

The influence of mechlorethamine (HN2, nitrogen mustard) on UV-induced carcinogenesis was examined in the hairless mouse skin in vivo. Noncarcinogenic amounts of topically applied HN2 and carcinogenic levels of UVB energy were used in the study. The HN2 applications significantly accelerated the appearance and growth of cutaneous tumors in this study. Thus HN2 acted as either a promoter or cocarcinogen for UV-induced cancer formation. Although the mechanism of this effect was not established, combinations of UVB radiation and HN2 topical therapy pointed to an increased incidence of cutaneous tumors in human skin.
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PMID:Effects of mechlorethamine (HN2, nitrogen mustard) on UV-induced carcinogenesis in hairless mouse skin. 658 24

The nitrate level of a nonfilter reference cigarette was elevated from 0.52% to 1.2, 1.8, 2.4 and 3.05%, respectively, by addition of sodium nitrate. Data from the mainstream smoke analyses of these cigarettes were compared. Yields of carbon monoxide and carbon dioxide were not significantly altered as a result of nitrate elevation. Tar, nicotine, benzo[a]pyrene (BaP) and catechol in mainstream smoke were reduced while yields of nitrogen oxides (NOx), volatile N-nitrosamines (VNA) and tobacco-specific N-nitrosamines (TSNA) were significantly increased. On the basis of previous bioassays with smoke condensates from high-nitrate cigarettes, it was expected that the cutaneous tumorigenicity of these tars would be reduced due to lower levels of BaP (and other carcinogenic PAH) and catechol. However, the total carcinogenic potential of whole smoke from high nitrate cigarettes is considered by us to be significantly increased due to the elevated yields of Nox, VNA and TSNA. The nitrosamines are regarded as a major group of carcinogens in tobacco smoke; the nitrogen oxides are the most important precursors for the endogenous formation of N-nitrosamines upon smoke inhalation. The findings of this model study support the recommendation that the nitrate content of tobacco products should be reduced.
Carcinogenesis 1984 Feb
PMID:Carcinogenic agents in cigarette smoke and the influence of nitrate on their formation. 669 39

The possibility of N-nitrosomorpholine formation was investigated in mice treated with morpholine and then exposed to 45 p.p.m. nitrogen dioxide in an inhalation chamber for 2 h. Following this treatment, the mice were frozen and pulverized in liquid nitrogen and concentrated extracts from the powders of these animals were analyzed for N-nitrosomorpholine using a thermal energy analyzer interfaced to a gas chromatograph. The data indicate that nitrogen dioxide exposure causes the nitrosation of morpholine in vivo. Additional data show that significant levels of artifactually formed N-nitrosomorpholine are found in control animals that are treated with morpholine after exposure to nitrogen dioxide for 2 h unless a combination of L-ascorbic acid and d,1-alpha-tocopherol are used to inhibit nitrosation during the homogenization, extraction, and analysis of the samples. The need for both a lipid phase nitrosation blocker (d,1-alpha-tocopherol) and an aqueous phase nitrosation blocker (L-ascorbic acid) indicates that the nitrosation of morpholine occurs in both a lipid and an aqueous phase in vitro and therefore may occur in both a lipid and an aqueous environment in vivo. The data from this study also demonstrate the importance of adding suitable inhibitors of nitrosation, such as L-ascorbic acid and d,1-alpha-tocopherol to the extraction solution to prevent possible artifactual formation of N-nitrosomorpholine during the extraction and analysis of the samples.
Carcinogenesis 1984 May
PMID:Formation of N-nitrosomorpholine in mice treated with morpholine and exposed to nitrogen dioxide. 672 75

Earlier observations that substitution of the aromatic nucleus of an arylamino/nitro carcinogen with either a sulphonic acid substituent or two methyl groups placed ortho to the nitrogen substituent renders the molecule non-carcinogenic have been extended via studies conducted in vitro. 4-Aminobiphenyl-4'-sulphonic acid has been synthesized and found to be non-mutagenic in the Salmonella mutation assay when tested under conditions where 4-aminobiphenyl was mutagenic. It is concluded that this sulphonic acid derivative may prove non-carcinogenic to rodents. In contrast to the non-carcinogenicity and non-mutagenicity reported for 3,3',5,5'-tetramethylbenzidine, 3,5-dimethyl-4-aminobiphenyl is approximately as mutagenic as 4-aminobiphenyl. It is therefore concluded that this material is potentially carcinogenic and that the loss of mutagenic activity observed for tetramethylbenzidine may be a structurally specific rather than a general phenomenon. In contrast, 3,5-dimethyl-4-nitrobiphenyl was much less mutagenic than 4-nitrobiphenyl. 9,9'-Bijulolidyl, a derivative of 3,3',5,5'-tetramethylbenzidine, was also found to be non-mutagenic. The general significance of these findings to the employment of structure-activity relationships in the design of non-mutagenic/non-carcinogenic molecules is discussed.
Carcinogenesis 1982
PMID:Evaluation of two suggested methods of deactivating organic carcinogens by molecular modification. 675 75

A u.v. sensitive Chinese hamster cell line V79/79 has been shown to be also more sensitive to methyl methanesulphonate (MMS) and nitrogen mustard (HN2) exposure than wild-type V79 cells. A comparison of the effects of the two alkylating agents on DNA synthesis measured by [3H]thymidine (TdR) incorporation into whole cells and by alkaline sucrose gradient sedimentation 14C-labelled template and of pulse labelled DNA revealed no significant differences between the responses of the two cell lines. The effects of a range of doses of both drugs on the rate of progress through the cell cycle was compared using cytofluorimetry. The more sensitive V79/79 cells failed to show a significant delay in progress through the cell cycle even at the highest doses tested (0.2 microM HN2 and 2.0 mM MMS). In contrast, V79 cells showed a marked S phase delay in response to both HN2 and MMS exposure. The possible relationships between failure to delay cell cycle progression, and cellular sensitivity are discussed.
Carcinogenesis 1983
PMID:The role of suppression of DNA synthesis and inhibition of cell cycle progression in cellular sensitivity to alkylation damage. 683 33

The study of the binding of the liver carcinogen, N-acetyl-2-aminofluorene, to the DNA of the target organ-as the probable initial step in the process of carcinogenesis-has shown that three modes of interaction occur. N-Acetyl-2-aminofluorene is covalently bound with the nitrogen to the carbon 8 of guanine (I) and with the 3-position to the free NH(2)-group of guanine (II). The third mode of interaction is formed by a covalent bond between the nitrogen of 2-aminofluorene and the carbon 8 of guanine (III). In this study the different modes of interaction were measured separately in stromal and parenchymal cells of the rat liver, after a single intraperitoneal dose. The DNA was isolated from nuclei that had been separated by 1g sedimentation. In parenchymal DNA the types of interaction I and III occur in the same amounts one day after application. In stromal cells the amount of interaction I is relatively small and interaction III predominates (ratio III:I = 5). The amount of interaction III in tetraploid hepatocytes (the largest cell population in the studied rats) per mg DNA is about two times higher than in the stromal cells. While the removal of the total amount of DNA-bound carcinogen takes place at the same rate in the two cell types, a difference in rate and efficiency of repair is observed for the different types of interaction. In tetraploid hepatocytes, interaction I is almost completely removed from the DNA 2 weeks after application, while interaction III diminishes to about 1/3 during the first week but the remaining part disappears very slowly. As shown in earlier studies, interaction II remains in the DNA at a constant level.
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PMID:Binding and repair of 2-acetylaminofluorene adducts in distinct liver cell populations. 683 99

Benzo[f]quinoline and benzo[h]quinoline are widespread environmental pollutants which have been found to be mutagenic. The metabolism of benzo[f]quinoline and benzo[h]quinoline was investigated using a liver homogenate from Aroclor-pretreated rats. The metabolites of benzo[f]quinoline which were identified were 7,8-dihydroxy-7,8-dihydrobenzo[f]quinoline, 9,10-dihydroxy-9,10-dihydrobenzo[f]quinoline, 7-hydroxybenzo[f]quinoline, and benzo[f]quinoline-N-oxide. Metabolism studies on benzo[f]quinoline performed in the presence of the epoxide hydratase inhibitor, 3,3,3-trichloropropylene oxide, demonstrated that the formation of both of these dihydrodiols can be inhibited. The major metabolites of benzo[h]quinoline were identified as 5,6-dihydroxy-5,6-dihydrobenzo[h]quinoline and 7,8-dihydroxy-7,8-dihydrobenzo[h]quinoline. Benzo[h]quinoline-N-oxide was not detected as a metabolite. In the presence of an epoxide hydratase inhibitor, the major metabolites of benzo[h]quinoline were 5,6-epoxybenzo[h]quinoline and 7-hydroxybenzo[h]quinoline. The difference in the metabolism to N-oxides observed between benzo[h]quinoline and benzo[f]quinoline is consistent with previous observations in which sterically hindered aromatic ring nitrogen compounds such as benzo[h]quinoline are more resistant to N-oxide formation. The nitrogen atom of these aza-arenes with its lone pair of electrons has a significant influence on sites at which dihydrodiols are formed. The data suggest that the aromatic ring nitrogen of these azaphenanthrenes has an effect similar to that of a methyl substituent in directing their metabolic oxidation.
Carcinogenesis 1983 Sep
PMID:Identification of the metabolites of benzo[f]quinoline and benzo[h]quinoline formed by rat liver homogenate. 688 36

E. coli DNA, labelled with [14C]adenine and [14C]-guanine, was allowed to react with the [3H]-labelled carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one in the presence of a microsomal metabolising system. Enzymatic hydrolysis of the DNA followed by Sephadex LH20 chromatography of its constituent nucleosides established that the major DNA - carcinogen adduct involved guanine, and not adenine. This was confirmed by submitting calf thymus DNA, which had been allowed to react with the unlabelled carcinogen, to pyrolysis electron impact mass spectrometry without further derivatisation. Analysis of a selected ion product (m/z 368) by means of mass-analysed kinetic energy spectrometry, a technique which allows study of the further fragmentation of the single, selected ion, revealed that the guanine moiety was attached via the nitrogen atom of its exocyclic amino group to C-1 of a 1,2,3,4-tetrahydro-2,3,4-trihydroxy derivative of the original carcinogen.
Carcinogenesis 1981
PMID:Mass spectral characterisation of the major DNA--carcinogen adduct formed from the metabolically activated carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one. 727 43


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