bluuebunny/crossref_metadata_2025_split huggingface dataset:
Living in a chemical world: Actions and reactions to industrial carcinogens
Authors: Infante Peter F. , Pohl Gwen K. 
Published: February 2006

AbstractThe synthesis of chemical substances has resulted in technological benefits for society and has also caused increased chemical exposures and risks of related cancers. Although progress has been made in cancer treatment, there has been little improvement in real survival time for people who develop the major forms. Therefore, the need to prevent cancer is paramount. The greatest chemical exposures and risk of associated preventable cancers are found in the workplace, but generally environmental exposures receive greater public attention.Chemical causes of cancer have been identified, and in some cases decades have passed before controls have been adequately instituted. Some companies show a high regard for worker health, while others may minimize or misrepresent the hazards to exposed workers. Medical personnel receive relatively little education in the recognition of industrially related diseases. Workers are often unaware of their risks or are trapped in jobs because of economic necessity, and government has been slow to regulate, in part because of lobbying efforts.Experience has shown that when chemicals are regulated relatively soon after they are identified as hazardous, lives are saved, and the industry is economically healthy; however, when regulation is delayed, thousands of people die unnecessarily, and the cost to industry and society are phenomenal. Society has the opportunity to apply the knowledge learned from these experiences as we address current problems of chemical pollution.
Beneficial effects of ascorbic acid on preimplantation mouse embryos after exposure to cyclophosphamide in vivo
Authors: Vogei Richard , Spielmann Horst 
Published: February 2006

AbstractTo study mechanisms of embryotoxicity in early pregnancy, we have evaluated the genotoxic and embryolethal effects of ascorbic acid (AA) alone or in combination with cyclophosphamide (CPA). Female mice were exposed on day 3 of pregnancy. Embryotoxicity was investigated at term and genotoxicity shortly after treatment using the chromosomal aberration test and the sister chromatid exchange (SCE) assay as sensitive end points. Additionally, cytotoxic effects were determined by a proliferation test. AA was not found to be embryotoxic, cytotoxic, or genotoxic when given alone. In combination with 10 mg/kg CPA, however, which induced 50% aberrant metaphases, 100% increase SCE frequency, and a strong inhibition of cell proliferation, AA in a dose range of 25–1,600 mg/kg did not change SCE and proliferation, but reduced the rate of aberrant metaphases significantly. This anticlastogenic effect was clearly correlated to a beneficial effect on embryolethality at term when 200 mg/kg ascorbic acid was given in combination with 40 mg/kg CPA.The results suggest that during early pregnancy AA is not genotoxic even at so‐called megadoses doses, but it seems to protect early embryos against damage induced by genotoxic agents like CPA.
Elevated expression of proto‐oncogenes accompany enhanced induction of heat‐shock genes after exposure of rat embryos in utero to ionizing irradiation
Authors: Higo Hiromi , Lee Juing Yi , Satow Yukio , Higo Ken‐Ichi 
Published: February 2006

AbstractWe have recently found that the effects of exposing rat embryos in utero to teratogens capable of producing cardiac anomalies were expressed later as enhanced induction of heat‐shock proteins (hsp70 family) when embryonic hearts were cultured in vitro. However, it remained to be determined whether heat‐shock proteins are induced in vivo after exposure to teratogens. The heat‐shock response in some mammalian systems is known to be accompanied by elevated expression of proto‐oncogenes. Using gene‐specific DNA probes, we examined the levels of the expression (transcription) of heat‐shock protein genes and two nuclear proto‐oncogenes, c‐fos and c‐myc, in the embryos removed from irradiated pregnant mother rats 4 or 5 days after the irradiation. We found that the levels of expression in vivo of the hsp70 and c‐myc genes in the irradiated embryos increased by approximately twofold as compared with those in the control. The expression in vivo of the c‐fos gene was not detected in either the irradiated or non‐irradiated embryos. After 0.5‐hr incubation in vitro of the embryos, however, the expression of the c‐fos gene in the irradiated embryos was highly enhanced whereas the control showed no changes. Although the exact functions of these gene products still remain obscure, the enhanced expression of hsp70 gene(s) and the nuclear proto‐oncogenes observed in the present study may reflect repair of intracellular damages and/or regeneration of tissue by compensatory cell proliferation, processes that may disturb the normal program of organogenesis.
Hydrogen peroxide mutagenicity towards Salmonella typhimurium
Authors: Kensese Sontin Mossanda , Smith Leland L. 
Published: February 2006

AbstractIn bioassays conducted under controlled, comparable conditions, weak direct mutagenicity responses were observed for hydrogen peroxide in the standard (Ames test) agar plate incorporation bioassay with Salmonella typhimurium strains TA97, TA98, TA102, and TA1537, in a 20 min preincubation test with strains TA97, TA98, TA100, TA102, TA1537, and TA1538, and in a liquid incubation modification using strain TA1537. These results conclusively demonstrate that hydrogen peroxide is a weak mutagen, especially in strains that are sensitive to oxidative damage under suitable bioassay conditions.
Micronucleus formation by benzene, cyclophosphamide, benzo(a)pyrene, and benzidine in male, female, pregnant female, and fetal mice
Authors: Harper Barbara L. , Ramanujam V. M. Sadagopa , Legator Marvin S. 
Published: February 2006

AbstractMale, female, pregnant female, and fetal ICR mice were compared for their acute sensitivity to four single doses of model carcinogens, as measured by micronucleus formation in polychromatic erythrocytes 24 h after treatment in adult bone marrow and fetal liver at days 17–19 of gestation. Cyclophosphamide caused a dose‐responsive increase in micronuclei in all groups, without a consistent difference based on gender or pregnancy. At doses of 50 and 75 mg/kg given orally to the pregnant female, the fetuses were three to six times as sensitive as was the mother. Benzo(a)pyrene showed a similarly increased sensitivity of the fetus relative to the other groups, although it is a much weaker clastogen. Benzidine did not cause an increase in micronuclei in any group, although it was thought that the fetal liver might have been sensitive enough to detect it, relative to adult bone marrow. Benzene caused much less response in females than in males and almost no response in pregnant females and their fetuses, even though pregnant females metabolized at least half as much of the total dose as did the males (as measured by the presence of urinary metabolites of benzene). No single metabolite of benzene in the urine was consistently correlated with micronucleus formation in the bone marrow. Several factors must be interacting in different ways for different chemicals to influence their clastogenicity.
Rapid evaluation of topoisomerase inhibitors: Caffeine inhibition of topoisomerases in vivo
Authors: Shin Cha‐Gyun , Strayer John M. , Wani Maqsood A. , Snapka Robert M. 
Published: February 2006

AbstractCaffeine was found to inhibit both type I and type II topoisomerases in vivo as judged by its effects on replicating simian virus 40 (SV40) chromosomes. The study was facilitated by the use of a rapid filter assay for the detection and characterization of topoisomerase inhibitors. The assay, which requires neither purified enzymes nor substrates, was able to identify both antagonists and poisons of type I and type II topoisomerases.
cytogenetic surveillance of workers exposed to genotoxic chemicals: Preliminary experiences from a prospective cancer study in a cytogenetic cohort
Authors: Sorsa Marja , Ojajärvi Anneli , Salomaa Sisko 
Published: February 2006

AbstractCytogenetic endpoints, conventionally chromosomal aberrations, and later sister chromatid exchanges and micronuclei have long been used to assess exposure of human populations to genotoxic agents. Although the adverse nature of somatic chromosome damage is recognized at the group level, no ill‐health manifestations have been causally related to cytogenetic damage at the individual level. In work‐related exposures, e.g., ethylene oxide, styrene, benzene, vinyl chloride, and alkylating anticancer agents have been shown to induce somatic chromosomal damage in several studies. For all of these, a carcinogenic risk to humans has also been documented.The possible association of somatic chromosome damage and cancer will be elucidated in a Nordic prospective study. The objective is to find out the significance of a high or low score in any of the cytogenetic parametres to risk of cancer. In the Finnish part of the cohort of 806 individuals, 10 cases of cancer were observed during the first follow‐up period. Although the cohort is young and the numbers small, a slightly significant (P = 0.04) trend was observed for individuals with cancer and a score of chromosomal aberrations. No trend was observed for sister chromatid exchanges.The application of cytogenetic surveillance is still not routine methodology, but it is useful and informative in carefully controlled study designs. Special efforts should be directed toward combining different disciplines, i.e., cytogenetics, adduct monitoring, and end‐effect epidemiology, in order to reach quantitativeness in risk assessment.
Cytotoxicity, anchorage‐independent growth, and DNA adduct formation in human neonatal fibroblasts by 1, 2, 3, 4‐tetrahydro‐7, 12‐dimethylbenz(a)‐anthracene (TH‐DMBA), its six aryl fluoro regioisomers, and an exo methylene tautomer
Authors: Kumari H. Lalitha , Milo George E. , Witiak Donald T. 
Published: February 2006

Abstract1, 2, 3, 4‐Tetrahydro‐7, 12‐dimethylbenz(a)anthracene (TH‐DMBA), its six possible fluoro‐substituted regioisomers, and the C‐7 exo methylene tautomer of the 11F derivative have been investigated for their cytotoxicity and for their ability to induce anchorage‐independent growth and to form adducts in human neonatal foreskin fibroblasts. All compounds tested exhibited a low level of cytotoxicity, determined as percent cloning efficiency, up to a final concentration of 30 μ/ml. Except for 5F‐TH‐DMBA and the C‐7 exo methylene tautomer, all compounds induced anchorage‐independent growth of neonatal foreskin fibroblasts in soft agar at all concentrations tested (1, 3, 10, and 30 μ/ml). The C‐7 exo methylene tautomer induced anchorage‐independent growth only at a concentration of 10 μ/ml. Among the compounds tested the 6F derivative was the most effective compound at 1 μ/ml. The D‐ring fluoro isomers induced anchorage‐independent growth at a frequency comparable to TH‐DMBA itself, with the 11F derivative being the least effective of the four D‐ring regioisomers. All compounds except 5F‐TH‐DMBA formed detectable adducts with cellular DNA as determined by 32P postlabeling procedures, when the cells were treated at 1 μ/ml. Two adducts were detected in cells treated with TH‐DMBA and four adducts were detected in DNA obtained from cells treated with 6F‐TH‐DMBA. The level of bonding for the D‐ring fluoro isomers was quantitatively less and sometimes qualitatively different than that for TH‐DMBA. For the D‐ring compounds, the ability to induce anchorage‐independent growth frequency correlated with the total quantity of adduct formed. The C‐7 exo methylene tautomer formed a single adduct and the level of bonding was less than one adduct per 109 nucleotides. Analysis of these results led to the proposal that the planar anthracene ring structure (rings B, C, and D) of TH‐DMBA and possibly oxidative metabolism at benzylic carbon 4 of the A‐ring are important to DNA bonding and initation of induction of anchorage‐independent growth.
Simultaneous induction of mutagenic and cancerogenic effects in T × HT mice with transplacental ethylnitrosourea treatment
Authors: Schmahl Wolfgang , Neuhäuser‐Klaus Angelika , Leierseder‐Bauer Maria , Luz Arne 
Published: February 2006

AbstractThe relationship between mutagenesis and carcinogenesis was investigated in T × HT crossbred mice using diaplacental application of ethylnitrosourea (ENU) at different stages of embryonal development. Mutagenesis was detected by induction of coat color spots, and the carcinogenic response was investigated in a long‐term follow‐up study of the F1‐generation. The animals were particularly sensitive to induction of tumors at the central nervous system (CNS)‐skull/vertebra interface (30% and 20% in ENU‐treated male and female offspring, respectively, compared with < 1% in controls). There was a correlation between the appearance of these tumors and the presence of color spots. This correlation was low but statistically significant in female offspring. Three other types of tumors showed a correlation with the presence of coat color spots. Liver tumors were significantly increased in color spot‐positive females but unchanged in males. Lung tumors were reduced in color spot‐positive males and appeared earlier in color spot‐positive females. There was a lower incidence of lymphoma/leukemia in all spot‐positive mice. The reduction in tumor incidence beyond the spontaneous rate in spot‐positive animals might be caused by a high cytolethal response to ENU in the relevant organs and tissues.
Mutagenic and teratogenic effects of cyclophosphamide on the chick embryo: Chromosomal aberrations and cell proliferation in affected and unaffected tissues
Authors: Novotná Božena , Jelínek Richard 
Published: February 2006

AbstractChromosomal aberrations and cell proliferation were analyzed in the chick embryo blood, limb bud, and facial tissues 12 and 24 hours after cyclophosphamide (CP) administration on day 3. The cytogenic findings were compared with teratogenic effects evaluated on incubation day 8. Low dose (0.3 μg) resulting in heart defects exclusively, increased the frequency of aberrant cells with simultaneous depression of cell proliferation in blood only. High dose of CP (6 μg), besides the heart defects, also induced facial clefts and limb malformations, and strong clastogenic effects associated with mitotic inhibition were observed in all tissues investigated. The results support the idea that the consequences of mutagenic action of cyclophosphamide—cell cycle delay and excessive death of cells with unstable aberrations—result in abnormal morphogenesis.
Dangerous properties of petroleum‐refining products: Carcinogenicity of motor fuels (Gasoline)
Authors: Mehlman Myron A. 
Published: February 2006

AbstractGasoline contains large numbers of dangerous and cancer‐causing chemicals such as benzene, butadiene, toluene, ethylbenzene, xylene, trimethyl pentane, methyltert‐butylether (MTBE) and many others. For the U.S. alone approximately 140 billion gallons of gasoline were consumed in 1989. An increase in only ten cents per gallon in price of gasoline generates 14 billion dollars in extra profit per year for oil industry cartel.Laboratory animals exposed to gasoline developed cancers in different tissues and organs. A number of epidemiological studies in humans provide evidence of increased cancer risk of leukemia, kidney, liver, brain, lymphosarcoma, lymphatic tissue pancreas and other tissues and organs.
Sensitivity of cultured lymphocytes from patients with nevoid basal cell carcinoma syndrome to ultraviolet light and phytohemagglutinin stimulation
Authors: Ferraro P. , Celotti L. , Furlan D. , Pattarello I. , Peserico A. 
Published: February 2006

AbstractDNA repair and replication after in vitro UV irradiation were determined in cultured peripheral blood lymphocytes from 6 patients with nevoid basal cell carcinoma syndrome (NBCCS) and from a group of control donors. DNA repair synthesis (UDS) was measured in unstimulated lymphocytes by incubation with 3H‐TdR in the presence of hydroxyurea for 3 and 6 h after UV irradiation (6‐‐48 J/m2). DNA replication was measured in PHA‐stimulated lymphocytes, UV‐irradiated or mock‐irradiated, by incubation with 3H‐TdR for 24 h. The effect of the mitogen was followed during 5 days after stimulation by determining the incorporation of 3H‐TdR, the increase of cell number, and the mitotic index. NBCCS and control lymphocytes showed equal sensitivity to UV light in terms of UDS and reduced response to PHA. On the contrary, the mitotic index and the number of cells in stimulated cultures were significantly lower in the affected subjects. These data suggest an altered progression along the cell cycle, which could be characteristic of stimulated NBCCS lymphocytes.
Evaluation of the genotoxicity of gentian violet in bacterial and mammalian cell systems
Authors: Aidoo Anane , Gao Ning , Neft Robin E. , Schol Henry M. , Hass Bruce S. , Minor Toni Y. , Heflich Robert H. 
Published: February 2006

AbstractPrevious studies indicate that gentian violet (GV), a triphenylmethane dye used in agriculture and human medicine, is a clastogen in vitro and a carcinogen in chronically exposed mice and rats. Data on its genotoxic activity, however, have been incomplete and partly contradictory. Mutagenesis and DNA damage experiments were conducted to re‐evaluate the genotoxic potential of GV in both bacterial and mammalian cell systems. GV was mutagenic in Salmonella typhimurium tester strains TA97 and TA104, but there was little mutagenic activity detected in strains TA98 and TA100. A rat liver homogenate fraction (S9) tended to increase mutagenicity. The major microsomal metabolites of GV, pentamethylpararosaniline and N,N,N′,N′‐tetramethylpararosaniline were less mutagenic in TA97 and TA104, while N,N,N′,N"‐tetramethylpararosaniline was a weak mutagen in Salmonella. GV was not mutagenic in Chinese hamster ovary (CHO) cell strain CHO‐K1‐BH4, and was a questionable mutagen in CHO‐AS52 cells. While GV produced DNA damage as measured by sedimentation of nucleoids derived from B6C3F1 mouse lymphocytes treated in vitro, no damage was found in lymphocytes isolated from mice dosed with GV. GV was also a weak producer of gene amplification in an SV40‐transformed Chinese hamster cell line. The results indicate that GV is a point mutagen in bacteria; however, since similar exposure conditions produced weak mutagenic activity in mammalian cells, GV may be carcinogenic by virtue of its clastogenic activity.
Interaction of drugs with extranuclear genetic elements and its consequences
Authors: Ebringer Libor 
Published: February 2006

AbstractBacterial ancestry of mitochondria and plastids is now generally accepted. Both organelles contain their own DNA and transcription‐translation apparatus of a prokaryotic type. Due to this fact these systems carry bacteria‐like properties. Thus organellar DNA and ribosomes are essentially different from nuclear DNA and cytoplasmic ribosomes in physical as well as in functional respects. Due to the bacterial character of both types of organelles they are susceptible to various antibacterial chemicals. Inhibitors of bacterial protein synthesis inhibit mitochondrial (plastidial) biogenesis. Therefore the cellular content of mitochondria (plastids)‐made proteins decreases during cytoplasmic turnover or cell division in the presence of these drugs. Such drug activity consequently leads to a reduced capacity for oxidative phosphorylation or photosynthesis. Organellar genomes are less stable and more sensitive to mutagenesis as compared to nuclear genome. It means also that genotoxic agents induce various disorders of mitochondrial (plastidial) functions. Impairments in the respiratory chain are associated with structural as well as functional abnormalities of mitochondria. These are clinically expressed mostly in tissues with a high demand for ATP: brain, heart, skeletal muscle, and retina. On the other hand, some antibacterial inhibitors of mitochondrial biogenesis (e.g., tetracyclines) inhibit selectively tumor cell proliferation. Therefore they may be considered for use in anticancer therapy.The article summarizes the response of mitochondria and plastids in various organisms to drugs and environmental xenobiotics. Various model organisms suitable for detection of xenobiotic effect on mitochondria (plastids) are presented as well as the possible consequences of such interaction.
Detection of 6‐thioguanine‐resistant spleen lymphocytes in different mouse strains by autoradiography
Authors: Hüttner Edith , Braun Rolf , Wielgosz Szesny M. , Schöneich Jörg 
Published: February 2006

AbstractThe variant frequencies for 6‐thioguanine‐resistant spleen cells in different mouse strains have been estimated by autoradiography for animals without chemical treatment and in cases of in vivo mutagen dosage with ethylnitrosourea and cyclophosphamide, respectively. In untreated mice, the following variant frequencies have been found: C57B1/6J, 2.84 × 10−5;NMRI, 3.04 × 10−5;DBA/2J, 5.91 × 10−5. The selective concentration of 6‐thioguanine was 100 μM for strains NMRI and DBA, while in the case of C57B1 with this concentration, no variant cells could be counted and a selective concentration of 50 μM was chosen. Treatment with 70, 140, and 210 mg/kg ethylnitrosourea resulted in increased variant frequencies in cells isolated 8 or 15 days later. On the other hand, doses of 20, 60, and 120 mg/kg cyclophosphamide did not result in a clear dose‐response relationship of variant frequency in cells isolated 1, 8, 15, 22, and 29 days after treatment. These data are discussed with respect to findings in human populations exposed occupationally to cyclophosphamide.
Rules of molecular geometry for predicting carcinogenic activity of unsubstituted polynuclear aromatic hydrocarbons
Authors: Flesher James W. , Myers Steven R. 
Published: February 2006

AbstractThe rules of molecular geometry for predicting carcinogenic activity of polynuclear aromatic hydrocarbons (PAH) have been applied to a series of 50 unsubstituted PAH, and predicted carcinogenic activity is in good agreement with the results of testing for complete carcinogenic activity in mice and/or rats. The rules were developed from a knowledge of the center or centers of highest chemical or biochemical reactivity and are consistent with a unified hypothesis which states that the first step in the metabolic activation of unsubstituted PAH is the biochemical introduction of a methyl group. This bioalkylation reaction 1) takes place between certain PAH and S‐adenosyl‐L‐methionine and is catalyzed by cytosolic methyltransferase, 2) offers a means of probing for centers of reactivity in PAH, 3) provides a biochemical link between unsubstituted preprocarcinogens of aromatic type ArX and alkyl‐substituted procarcinogens of aromatic type ArCH2X (where X = H), and 4) makes it possible to include compounds of both aromatic types, in a consistent theory of aromatic hydrocarbon activation which incorporates alkyl substitution. The present study reveals that there are structural determinants of carcinogenicity.