bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic effects of deoxyribonucleotide pool imbalances
Authors: Kunz Bernard A. 
Published: February 2007

AbstractIn vivo DNA precursor imbalances can have profound genetic consequences in prokaryotes and eukaryotes. In vitro studies have demonstrated that DNA replication fidelity is dependent on correct balances of deoxyribonucleoside triphosphates during DNA synthesis. These findings suggest that intracellular concentrations of DNA precursors may be regulated in order to minimize the frequency of genetic change. In addition, they indicate the existence of important nonDNA targets for the induction of mutation, recombination, chromosome aberrations, etc. In this article, the genetic effects of deoxyribonueleotide pool imbalances are reviewed.
The hepatocyte primary culture/DNA repair assay using mouse or hamster hepatocytes
Authors: McQueen Charlene A , Kreiser Dawn M , Williams Gary M. 
Published: February 2007

AbstractThe hepatocyte primary culture (HPC)/DNA repair assay using rat hepatocytes was developed to identify genotoxic chemicals. Since there are species differences in susceptibility to chemical carcinogens, it was desirable to extend the assay to other species. Carcinogens and noncarcinogens from six structural classes were tested with hepatocytes from B6C3F1 mice or Syrian hamsters. In hepatocytes from both species, DNA repair was elicited by the carcinogens methyl methanesulfonate, aflatoxin B1, 2‐acetylaminofluorene, benzo(a)pyrene, dimethylnitrosamine, nitrosopyrrolidine, 3'‐methyl‐4‐dimethylaminoazobenzene, and p‐dimethylaminoazobenzene. With aflatoxin B1, mouse hepatocytes required a dose of 10−4 M for a maximum response while only 10‐6 was needed for hamster hepatocytes. All the presumed noncarcinogens, except 4‐dimethylaminoazoben‐zene‐4'‐sulfonyl chloride, were negative in mouse hepatocytes. This chemical, as well as aflatoxin G2 and pyrene, which have not been tested for carcinogenicity in the hamster, were positive in hamster hepatocytes. These findings demonstrate that genotoxic chemicals can be identified by the HPC/DNA repair assay using hamster or mouse hepatocytes. Furthermore, in vivo differences in susceptibility to chemical carcinogens such as aflatoxin B are reflected in the in vitro assay.
5‐nitroacenaphthene: A newly recognized role for the nitro function in mutagenicity
Authors: McCoy Elena C. , de Marco George , Rosenkranz E. Joshua , Anders Monika , Rosenkranz Herbert S. , Mermeistein Robert 
Published: February 2007

AbstractThe direct‐acting mutagenicity of 5‐nitroacenaphthene for Salmonella typhimurium is dependent upon the reduction of the nitro function as evidenced by the significant decrease in mutagenicity seen with nitroreductase‐deficient Salmonella strains. Addition of microsomal preparations results in a significant increase in mutagenicity and a by‐passing of the block in nitroreductase‐deficient and arylhy‐droxylamine esterifying‐deficient enzyme strains. The results are taken to indicate that the microsome‐induced mutagenicity is due primarily to oxidation of the acenaphthene moiety. The results are consistent with recent studies which indicate that the nitro function exercises a directing effect on ring oxidation.
Induction of ouabain‐resistant mutants by chemical carcinogens in rat prostate epithelial cells
Authors: Link Karl H. , Heidelberger Charles , Landolph Joseph R. 
Published: February 2007

AbstractWe determined optimal conditions to quantitatively select ouabain‐resistant (Ouar) mutants induced by chemical carcinogens in a rat prostate epithelial cell line (RPYK). These conditions included selection of Ouar mutants in 3 mM ouabain, an expression time of two days following a two‐day treatment with carcinogens, and a reseeding density of 2 × 105 mutagenized cells per 100 mm dish to select mutants in ouabain. Ouar mutants induced by N‐methyl‐N'‐nitro‐N'‐nitrosoguanidine (MNNG) remained stably Ouar when passaged in nonselective medium. Hemicyst formation, a characteristic of epithelial cells, was reversibly inhibited by ouabain in wild‐type cells and was resistant to ouabain in Ouar cells. The direct‐acting carcinogens MNNG and methylazoxymethanol‐acetate (MAMA) and the environmentally widespread procarcinogens aflatoxin B1 and benzo(a)pyrene increased the frequency of Ouar mutants in RPYK cells. The procedures developed here now make it possible to detect some environmental carcinogens likely to cause prostate cancer by virtue of their ability to mutate cultured prostate epithelial RPYK cells. The sensitivity of the RPYK cell line to aflatoxin‐induced cytotoxicity and mutagenesis also makes it a useful cell system in which to study enzymes governing the conversion of aflatoxin to genotoxic metabolites.
Synergism in the transformation of hamster embryo cells treated with formaldehyde and adenovirus
Authors: Hatch George G. , Conklin Patricia M. , Christensen Carla C. , Casto Bruce C. , Nesnow Stephen 
Published: February 2007

AbstractFormaldehyde is a large production volume chemical widely distributed in research laboratories, industrial workplaces, and home and personal environments. Inhalation studies with formaldehyde have documented its ability to produce squamous cell carcinomas in rats. When primary hamster embryo cells were treated by gaseous exposure to formaldehyde or by incorporation into the medium, a dose‐related increase in the frequency of SA7 virus transformation was produced. The length of chemical treatment and the time interval before subsequent addition of transforming virus was critical, with two‐hr treatment times as the most efficient. Treatment by gaseous exposure permitted utilization of lower treatment concentrations. Determination of formaldehyde concentrations in culture media of bioassay dishes treated by this method documented that 2.2 fig/ml produced significantly enhanced viral transformation. Exposure of hamster embryo cells to formaldehyde by these methods produces reproducible and quantitative genotoxic effects.
Effects of antimutagens on prophage induction in E coli lysogenic for lambda
Authors: Persons Diane L. , Shankel Delbert M. 
Published: February 2007

AbstractThe effects of caffeine, acriflavine, spermine, quinacrine, and adenosine on spontaneous and UV‐induced prophage induction in repair‐proficient and ‐deficient strains of lysogenic Escherichia coli were examined. Caffeine caused a coinducing effect on UV induction in KMBL 160 (repair proficient) and KMBL 163 (uvrA), an anti‐inducing effect in KMBL 161 (uvrE), and had no detectable effect in KMBL 164 (uvrC). Acriflavine increased UV induction in KMBL 160 and decreased it in all three repair‐deficient mutant strains. Spontaneous induction was reduced by acriflavine in all four strains. Spermine caused a decrease in UV induction in KMBL 160 and KMBL 164, while it had limited effect in KMBL 161 and KMBL 163. For spontaneous induction spermine caused an increase in KMBL 160 and KMBL 163, a decrease in KMBL 164 and no detectable effect in KMBL 161. Quinacrine had no significant effect on spontaneous induction in KMBL 160 and KMBL 164, but caused a decrease in spontaneous induction in KMBL 161 and KMBL 163. Quinacrine produced no effect on UV induction in KMBL 160; however, it decreased UV induction in the three repair‐deficient strains to some extent. A significant increase in spontaneous induction in KMBL 160 was caused by adenosine, while it had little effect in the repair‐deficient strains. UV induction was not affected by adenosine.
Mutagenic activity from nitrosation of oligoamines
Authors: Murphey‐Corb Michael , Kong Hay‐Long , Murray Michael L. 
Published: February 2007

AbstractTo determine structural features necessary for the production of direct mutagenic activity from oligoamine‐nitrate reaction mixtures, we systematically tested a group of aliphatic amine substrates for comutagenic action with nitrite. The ability to react with nitrite and form direct‐acting mutagenic derivatives was common to a reasonably well defined class of aliphatic polyamines. In general, primary‐secondary diamino compounds were mutagenic in the Ames Salmonella tester system when reacted with nitrite, whereas primary and secondary amines produced no direct mutagenic activity when tested separately. In combination with teritary amino groups, primary amines were inactive; one secondary‐tertiary amine was tested, and this substrate produced mutagenic activity.
Review: Putative mutagens and carcinogens in foods. I. Nitrate/nitrite ingestion and gastric cancer mortality
Authors: Hartman Philip E. 
Published: February 2007

AbstractPublished figures for per capita daily levels of nitrate ingestion in the 1970s are compared with gastric cancer mortality estimates for the same period. A strong positive correlation is observed in 12 countries, not only when the data are analyzed as a linear—linear function, as illustrated in this paper, but also when the relationship is analyzed as a function of (nitrate)2. This correlation supports the concept that important components of gastric cancer induction are the in vivo bacterial reduction of nitrate to nitrite and the intragastric formation of mutagenic/ carcinogenic nitroso, and possibly nitro compounds. Data are summarized from a recent National Academy of Sciences [1981] study that enumerates by individual dietary sources the mean ingestion of nitrate and nitrite by the United States population at the present time. The ingestion figures are used to calculate the probable current gastric nitrite load in US adults with normal gastric acidity. Similar calculations are provided for past years (1925, 1936–1937, and 1971–1972). Since 1925, there has been an approximately threefold decrease in gastric cancer mortality in the US, and this decline is paralleled by an approximately fourfold decrease in average gastric nitrite load. The excessive ingestion of nitrate/ nitrite in the US in past years is attributed to the very high content of nitrate and nitrite in cured meats. Several ways compatible with current US farming and marketing practices that are capable of reducing the gastric nitrite load even further are pointed out.
The induction of chromosome aberrations by cis‐platinum(II) diamminodichloride in drosophila melanogaster
Authors: Brodberg R. K. , Lyman R. F. , Woodruff R. C. 
Published: February 2007

AbstractWe have determined the in vivo effects of cis‐platinum(II)diarnminodichloride (cis‐PDD) treatment on the induction of chromosome aberrations in Drosophila melanogaster germ cells. cis‐PDD treatment induces significant increases in chromosome breakage in all stages of spermatogenesis in a battery of test systems using ring or rod‐X males and repair‐proficient or deficient females. Since no increase in nondisjunction was induced by cis‐PDD in either male or female germ cells, any aneuploidy inducing effects of this compound should result from its clastogenic action. We also find that mei‐9 excision repair function is involved in the repair of cis‐PDD‐induced DNA lesions in a manner that provides additional evidence that partial and ring chromosome losses are not completely homologous.
Rat nasal tissue activation of benzo(a)pyrene and 2‐aminoanthracene to mutagens in salmonella typhimurium
Authors: Bond James A. , Li Albert P. 
Published: February 2007

AbstractCytochrome P‐450‐dependent monooxygenase activity has been measured in the nasal turbinates of dogs and rats. The capacity of male Fischer‐344 rat nasal tissue to bioactivate benzo(a)pyrene (BaP) and 2‐aminoanthracene (2‐AA) to mutagens in Salmonella typhimurium was investigated. 2‐AA was mutagenic in strains TA98 and TA 100 when nasal tissue S‐9 was utilized as the activating enzyme system and BaP was mutagenic in strain TA 100. At all doses and protein concentrations tested, 2‐AA displayed nearly 500–1000 times greater bacterial mutagenicity than BaP. In strain TA‐100, nasal tissue S‐9 was approximately twice as active toward 2‐AA as lung S‐9 and 75% as active as liver S‐9. Aryl hydrocarbon hydroxylase activity was detected in rat nasal tissue when 14C‐BaP was used as a substrate. Rat nasal tissue metabolized BaP to several oxidized metabolites which included dihydrodiols, quinones, and phenols. 3‐Hydroxybenzo(a)pyrene and BaP‐3,6‐quinone were the major metabolites detected (150 pmoles/mg protein/30 min). These results indicate that rat nasal tissue can metabolize promutagens to reactive species which may play an important role in xenobiotic‐induced nasal tumors.
Review: Putative mutagens and carcinogens in foods III. Butylated hydroxytoluene (BHT)
Authors: Malkinson Alvin M. 
Published: February 2007

AbstractAlthough the average American's daily consumption of BHT can be measured in milligrams, there are numerous reports that BHT causes organ damage in laboratory animals. Only a few genotoxic effects of BHT have been reported, however, including mutagenicity in the abnormal sperm assay and ambiguous results regarding its teratogenicity. More dramatic are the modulatory effects of BHT on the actions of established mutagens and carcinogens. BHT can either enhance or inhibit mutagenic potency, depending on the substance tested. For example, in the Ames test, BHT is antimutagenic towards benzo(a)pyrene, but increases the number of Salmonella revenants induced by aflatoxin B1. BHT is one of the few compounds to have both tumor prophylactic and tumor promoting capacities. It is the temporal sequence in which BHT and carcinogens are administered to test animals which determines how BHT affects the response to these carcinogens. In common with other antioxidants, BHT inhibits the ability of carcinogens to induce tumors in various rodent organs when the animal is given BHT prior to carcinogen treatment. Unlike other antioxidants, however, the number of tumors increase when BHT is administered after carcinogen exposure. The comutagenic and cocarcinogenic properties of BHT have been demonstrated in tests ranging from the Ames test to cell transformation procedures to in vivo assays. These effects are probably mediated by metabolites of BHT, rather than by BHT itself.
Inhibitors of poly(ADP‐ribose) polymerase enhance DNA strand breaks, excision repair, and sister chromatid exchanges induced by alkylating agents
Authors: Park Sang Dai , Kim Chul Geun , Kim Moon Gyo 
Published: February 2007

AbstractBenzamide and 3‐aminobenzamide, inhibitors of poly(ADP‐ribose) polymerase, synergistically enhanced the frequencies of unscheduled DNA synthesis and sister chromatid exchanges in Chinese hamster ovary (CHO) cells treated with N‐methyl‐N'‐nitro‐N‐nitrosoguanidine (MNNG). These inhibitors also increased methyl methanesulfonate (MMS)‐ or MNNG‐induced DNA strand breaks and significantly retarded the rejoining of strand breaks in CHO and HeLa S3 cells. These results suggest that poly(ADP‐ribose) is important in the repair of DNA damage after exposure to alkylating agents and exercises a regulatory role in stabilizing chromatin structure whenever strand breaks occur in DNA.
Mutagenicity evaluation of amino‐oxazoline derivatives using in vitro and in vivo short‐term tests
Authors: Suter W. , Jaeger I. , Racine R. R. , Donatsch P. , Neumann P. , Matter B. E. 
Published: February 2007

AbstractDuring routine investigation of potential drugs it was found that 1‐methyl‐4‐(2‐oxazoline‐2‐ylamino)‐indazole (<1) compound 1 was mutagenic for Salmonella typhimurium TA 1535 and TA 100. The genotoxicity of compound 1 was confirmed by the following in vitro test systems: V79 Chinese hamster cells (HGPRT‐locus), Saccharomyces cerevisiae D7 (mitotic gene conversion, mutations, aberrations), and Escherichia coli (rec‐assay). On the other hand, when compound 1 was tested in vivo (micronucleus test in mice and sister chromatid exchange in Chinese hamsters) it did not show evidence of genotoxic activity. In order to study structure/activity relationships, different analogues of compound 1 were tested in Salmonella typhimurium TA 1535. The tests showed that (1) most 2‐amino‐oxazolines were mutagenic for the test organism; (2) the 2‐amino‐imidazoline and 2‐amino‐thiazolidine derivatives tested were not mutagenic; (3) substituents bound to the extranuclear nitrogen of the 2‐aminooxazoline ring had only a weak influence on the mutagenic potential; and (4) methylation of the oxazoline ring, most conspicuously at the carbon in position 5, strongly reduced the mutagenic effect. From these observations it is concluded that the reaction of nucleophilic DNA sites with the most electrophilic site of the oxazoline ring, ie, the carbon in position 5, is responsible for the genotoxicity of amino‐oxazoline compounds. Due to the genotoxicity observed in these in vitro tests this class of compounds was no longer developed, but dropped, even without performing a long‐term carcinogenicity study or considering the negative in vivo findings.
The effect of culture conditions and toxicity on the ames salmonella/microsome agar incorporation mutagenicity assay
Authors: Kazmer Sonja , Katz Marion , Weinstein David 
Published: February 2007

AbstractVarious methods were used to reconstruct an environment similar to a chemically bactericidal or bacteriostatic effect in the Ames mutagenicity assay in order to determine whether a false‐positive result could occur. Neither population reduction, sonication, nor increased histidine produced an increase of spurious revertant colonies.
Evaluation of the release of mutagens and 1‐nitropyrene from diesel particles in the presence of lung macrophages in culture
Authors: King Leon C. , Loud Kenneth , Tejada Silvestre B. , Kohan Mike J. , Lewtas Joellen 
Published: February 2007

AbstractThe release and recovery of mutagenic activity and 1‐nitropyrene from diesel particles phagocytized and cultured with lung macrophages were studied. The Ames Salmonella typhimurium plate incorporation assay was used to measure mutagenic activity. Quantitative analysis of 1‐nitropyrene was performed with liquid chromatography/fluorescence analysis. The cytotoxicity and phagocytosis of diesel particles with and without fetal calf serum were evaluated to select exposure concentrations that resulted in minimal toxicity and maximal engulfment of particles by the macrophages. The diesel‐particle exposure concentrations for the mutagenicity studies were 200 μg/ml in the absence of serum and 375 μg/ml in the presence of serum. Engulfment and incubation of diesel particles with lung macrophages resulted in the loss of considerable mutagenic activity (97–98%) and significantly less 1‐nitropyrene (10–25%). These studies suggest that lung macrophages have the capability to metabolize mutagenic nitroaromatics found in diesel particles.
Effect of BrdUrd and low doses of gamma radiation on sister chromatid exchange, chromosome breaks, and mitotic delay in mouse bone marrow cells in vivo
Authors: Morales‐Ramírez Pedro , Vallarino‐Kelly Teresita , Rodriguez‐Reyes Regina 
Published: February 2007

AbstractWe have measured, in mouse bone marrow cells in vivo, the ability of low doses of gamma radiation to induce sister chromatid exchanges (SCEs) in unifilarly 5‐bromodeoxyuridine (BrdUrd)‐substituted DNA. Also examined was the effect of BrdUrd incorporation on SCE induction by radiation, the comparative frequency of SCE and chromosome breaks induced by gamma radiation, the ability of ionizing radiation to interfere with normal cellular proliferation, and the relationship between proliferative inhibition and SCE and chromosome break frequency. A direct relationship between the number of SCEs and gamma radiation dose was observed, an effect which was dependent on BrdUrd incorporation. The frequency of SCE was 80 times higher than that of chromosome aberrations in cells with BrdUrd‐substituted DNA, and there was no difference between the frequency of SCE in cells with or without chromosome breaks. The mitotic delay increased with the time between irradiation and harvesting. There was no relationship between the extent of mitotic delay and the number of SCEs.
Characterization of automotive emissions by bacterial mutagenesis bioassay: A review
Authors: Claxton Larry D. 
Published: February 2007

AbstractDue to the growing numbers of diesel passenger automobiles in the United States, there has been an expanded effort to understand the health effects of airborne pollutants arising from increased automotive emissions. Bacterial mutagenicity testing has played an important role in the characterization of genotoxic effects and components arising from these combustion products. This review examines published material concerning the bacterial mutagenicity of automotive emissions. In addition, the paper explores factors that modify the mutagenicity of mobile‐source emissions, the use of bacterial tests for the comparison of various mobile source emissions, and the use of bacterial tests to examine the phenomena of mammalian uptake and metabolism.
Sequestration and release of polycyclic aromatic hydrocarbons by vertebrate cells in vitro
Authors: Kocan R. M. , Chi E. Y. , Eriksen N. , Benditt E. P. , Landolt M. L. 
Published: February 2007

AbstractVertebrate fibroblasts grown in vitro and exposed to various concentrations of the mutagen/carcinogen benzo(a)pyrene (B(a)P) internalized the compound and re‐crystallized it in lysosomes by 6–18 h postexposure. This phenomenon occurred when B(a)P at or above 10 μg/ml was introduced to the culture medium in a solvent such as DMSO or acetone but not when introduced dissolved in serum. Likewise, high fetal bovine serum concentrations in the culture medium (>20%) as well as human serum (10%) inhibited crystal formation, presumably owing to lipid competition for the compound. Electron‐microscopic observations of the cells during the uptake and crystal forming periods revealed that the cell membrane became altered within 3 h of exposure to B(a)P. This was followed by a return to normal of the membrane and the appearance of vesicles within the cell by 6–8 h. The vesicles then became filled with crystals which continued to grow while in the presence of B(a)P and disappeared when the cells were exposed to B(a)P‐free culture medium or serum lipids. Introduction of B(a)P into culture medium containing delipidated serum resulted in crystal formation indistinguishable from that which occurred when whole serum was present. Crystals were not formed when total lipoprotein and the lipoprotein components VLDL, LDL, HDL2, and HDL3 were used as solvents for B(a)P. The process of crystal formation was inhibited by the addition of 10−3 M KCN, and removal of the crystals was dependent on the concentration of lipoprotein in the culture medium.
The mutagenic activity of 5‐bromo‐2′‐deoxyuridine (BrdU) in vivo in rats
Authors: Maier P. , Weibel B. , Zbinden G. 
Published: February 2007

AbstractBrdU tablets were implanted subcutaneously in rats, and BrdU concentrations were determined in the serum. Within 5 hr peak concentrations of 10 μg BrdU/ml blood were reached. The influence of BrdU in vivo on cell cycling, DNA synthesis, spontaneous sister chromatid exchange (SCE) frequencies, and gene‐mutation frequencies (6‐TGr) was determined in freshly isolated cells from a subcutaneous granulation tissue. The most significant effect of BrdU in vivo was a doubling of the spontaneous 6‐TGr frequency.In reconstruction experiments in vitro the mutagenic activity of BrdU applied in concentrations found in vivo was 2.5–6‐fold higher.With the use of agar‐coated tablets, BrdU concentrations in the blood were reduced by half, and no peak concentration was found. The differential staining of chromatids was still sufficient. Since the mutagenic effect of BrdU in vitro was found to be strongly concentration dependent, the use of agar‐coated tablets is recommended in experiments in which the compound is used to demonstrate SCE in vivo.