摘要:

AbstractKeratinocytes from mouse skin were cultured for a short period in vitro following single or multiple treatments at low dose levels in vivo with the known chromosome‐damaging agent triethylenemelamine (TEM). The chemical was applied to the skin of HRA/Skh hairless mice at concentrations corresponding to those reported to initiate cancer in initiation‐promotion assays. A significant dose‐related depression in keratinocyte cell recovery occurred over the dose range 0.3–1 mg TEM/mouse (single or multiple treatments). Under the same conditions, a dose‐related induction of micronuclei was observed using the cytokinesis‐block method with cytochalasin B. A similar frequency of micronuclei was detected in binucleate cells from mice treated with single or multiple applications of TEM. Mice held for 12–48 h post‐treatment, before removal of skin for in vitro culture, yielded highest micronuclei frequencies. These results indicate that the same target cell population, skin keratinocytes, can be used to investigate both genotoxicity and carcinogenesis, and that micronucleus induction in these cells may be a sensitive signal of skin ca

ISSN:0893-6692    

DOI:10.1002/em.2850140102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractWe studied the effects of the inhibitor of DNA methylation, 5‐azacytidine (Aza‐C), alone and in combination with three antitumor alkylating agents, on sister chromatid exchanges (SCEs) and lymphocyte proliferation kinetics. Aza‐C was found to act synergistically on induction of SCEs when administered in combination with either melphalan (MEL) or chlorambucil (CBC) orcis‐platinum‐(ll)diamine dichloride (cis‐Pt). Cell‐division delays were consistently observed in cultures treated with each of the antineoplastics when introduced concomitantly with Aza‐C, compared with cultures treated with antineoplastics alone. Mitotic indices (Ml) in cultures treated with each of the three alkylating agents were found to be suppressed by Aza‐C. These results support the premise that hypomethylation of DNA causes cytotoxic effects by interfering with DNA repair mechanisms and by inhibiting DNA synthesis, or other cell growth mechanisms, which human lymphocytes undertake after being dama

ISSN:0893-6692    

DOI:10.1002/em.2850140103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractMutagenicN‐nitroso compound formation from the in vitro reaction of amebicides and anthelmintic drugs, which are pyrimidine derivatives or contain secondary aliphatic amines or heterocyclic nitrogens, has been previously described (Arriaga Alba et al.:Environmental and Molecular Mutagenesis12:65–73, 1988). Under similar conditions, antiparasitic drugs containing halogenated derivatives of tertiary amines or quaternary ammonium salts do not form mutagenic nitrosated compounds. In the present study the mutagenic activity of mouse urine was determined after oral administration of sodium nitrite and the two above‐mentioned groups of drugs (pyrantel pamoate, chloroquine, piperazine anddehydroemetine/iodochlorhydroxyquin and bephenium hydroxynaphthoate, respectively). Results show that the simultaneous administration of piperazine or chloroquine with sodium nitrite produced urinary mutagens that appeared conjugated as glucuronides, whereas pyrantel pamoate and dehydroemetine in the presence of nitrite caused only slightly mutagenic urine. No mutagenic activity was detected in the urine of mice to which halogenated derivatives of tertiary amines (iodochlorhydroxyquin) or quaternary ammonium salts (bephenium hydroxynaphthoate) were administered together with ni

ISSN:0893-6692    

DOI:10.1002/em.2850140104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractUrine from cigarette smokers was prepared for mutagenicity testing by extracting mutagens with solid‐phase extraction columns. Commercially available prepacked bonded silicas (octadecyl, cyclohexyl, cyanopropyl) were compared for their ability to concentrate the urinary mutagens. Recovered urinary metabolites were evaluated for mutagenic activity by using a microreversion assay withSalmonella typhimurium.Dose‐response data indicated that while mutagens were recovered by all three adsorbents, samples prepared by using the bonded cyanopropyl columns yielded the most bioactivity and/or the least amount of test organism toxicity. Varying pH of the urine was found to influence only the basified samples in terms of mutagenic recovery with the cyanopropyl base. Combinations of different adsorbents were not found to offer significant advantages over use of a singular extraction adsorb

ISSN:0893-6692    

DOI:10.1002/em.2850140105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractTo determine accurately the potential genetic damage induced by toxic inhaled agents, the cells that receive a high concentration of such agents should be analyzed. Pulmonary alveolar macrophages (PAMs) represent such cells. We compared the cytogenetic effects of cigarette smoke on PAMs of rats exposed repeatedly by different methods. This study was part of a larger investigation of the health effects resulting from different methods of exposing rats to cigarette smoke. Fischer 344/N male rats (4/group) were randomly selected from five different exposure groups: (1) nose‐only sham‐exposed (air) control, (2) whole‐body sham‐exposed control, (3) nose‐only intermittent, (4) nose‐only continuous, and (5) whole‐body continuous. The rats were exposed 6 hr/day, 5 days/week for 22–24 days. All smoke‐exposed rats received the same daily concentrations x time product (600 mg.hr.m−3for the first week, 1200 mg.hr.m−3thereafter) of cigarette smoke. Rats were injected intraperitoneally with colchicine at the end of exposure. PAMs were obtained by lung lavage and chromosomal damage was measured. Highly significant smoke‐induced differences in both structural and numerical aberrations were observed in continuously exposed rats vs. sham controls, regardless route of exposure. The structural aberrations observed were chromatid‐type deletions. Both hypoploid and hyperploid cells were detected. Our data suggest that cigarette smoke is clastogenic and may disrupt spindle‐fiber formation. These activities may play a role in the induction of human carcinogenesis caused

ISSN:0893-6692    

DOI:10.1002/em.2850140106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractThe present investigation describes a method for the detection of minute amounts of 3‐amino‐1, 4‐dimethyl‐5H‐pyrido[4, 3‐b]indole (Trp‐P‐1), a carcinogenic tryptophan pyrolysate, bound to the hemoglobin of erythrocytes and plasma from rabbits dosed orally with the dietary carcinogen. The method consists of the acid‐induced release of the dietary carcinogen adducts as the free carcinogen and their extraction with methylene chloride and subsequent quantitation by high‐performance liquid chromatography (HPLC). With this method, Trp‐P‐1 levels in plasma, platelets, and red blood cells were monitored for 12 weeks to determine a suitable indicator for estimating the exposure levels of the dietary carcinogen. The results suggest that Trp‐P‐1 in red blood cells that bound covalently to the hemoglobin is the most suitable for monitoring th

ISSN:0893-6692    

DOI:10.1002/em.2850140107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractAnthraquinones (AQs) comprise one important class of secondary metabolites predominantly produced by fungi and higher plants but also produced by a variety of other organisms. Humans orally ingest AQs from environmental sources as well as through direct use as nonpre‐scription laxatives, and some AQ derivatives are used as topically applied antipsoritic agents. Some AQs are mutagenic. We present evidence that aqueous solutions of several AQs in the presence of an appropriate reducing agent and dissolved oxygen generate superoxide when they are illuminated with broad‐spectrum light. Redox cycling of AQs could be responsible for some aspects of their toxicity in biological syst

ISSN:0893-6692    

DOI:10.1002/em.2850140108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

摘要:

AbstractTo evaluate a short‐term epithelial cell assay system to detect respiratory carcinogens, primary cultures of rat tracheal epithelial cells were exposed to a series of 17 compounds and scored for morphologically transformed cell colonies 28 days later. The test compounds included known carcinogens and noncarcinogens in volatile or liquids form. Tracheal epithelial cells were isolated from F344 rats, plated onto collagen‐coated dishes, and exposed to the test compounds on day 1 for 24 hours. At day 30 the cultures were fixed, stained, and scored for colonies having a density greater than 1,300 cells/mm2. With standardized protocols, such colonies are very infrequent in media and sol‐vent control cultures. Concentration levels for each chemical were chosen over a range from nontoxic to toxic levels. Highly positive compounds in this assay included benzo(a)pyrene, benzo(l)acean‐thrylene, 3‐methylcholanthrene, and formaldehyde. Compounds which were negative in this assay included pyrene, benzo(e)pyrene, and 4‐nitroquinoline‐N‐oxide. Examining the concordance of in vitro results with whole animal car‐cinogenesis studies revealed an accuracy of 88% with one false‐positive and one false‐negative compound. The results of these studies indicate that the rat tracheal epithelial cell assay may be useful in identifying potential respiratory carcinoge

ISSN:0893-6692    

DOI:10.1002/em.2850140109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850140110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY

ISSN:0893-6692    

DOI:10.1002/em.2850140111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1989

数据来源: WILEY