The application of mutagenicity tests to the prediction of carcinogenic activity of chemicals and drugs

AbstractThe purpose of this paper is to report on an expert system in design that screens for potential hazards from environmental chemicals on the basis of structure-activity relationships in the study of chemical carcinogenesis, particularly with respect to analyzing the current state of known structural information about chemical carcinogens and predicting the possible carcinogenicity of untested chemicals. The structure-activity tree serves as an index of known chemical structure features associated with carcinogenic activity. The basic units of the tree are the principal recognized classes of chemical carcinogens that are subdivided into subclasses known as nodes according to specific structural features that may reflect differences in carcinogenic potential among chemicals in the class. An analysis of a computerized data base of known carcinogens (knowledge base) is proposed using the structure-activity tree in order to test the validity of the tree as a classification scheme (inference engine).

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The Effects of Conjugated Linoleic Acids on Cancer

Processes ◽

10.3390/pr9030454 ◽

2021 ◽

Vol 9 (3) ◽

pp. 454 ◽

Cited By ~ 1

Author(s):

Marko Dachev ◽

Jana Bryndová ◽

Milan Jakubek ◽

Zdeněk Moučka ◽

Marian Urban

Keyword(s):

Potential Effect ◽

Conjugated Linoleic Acids ◽

Carcinogenic Activity ◽

Beneficial Effects ◽

True Value ◽

Ruminant Animals ◽

Anti Oxidant ◽

Cancer Agent

Conjugated linoleic acids (CLA) are distinctive polyunsaturated fatty acids. They are present in food produced by ruminant animals and they are accumulated in seeds of certain plants. These naturally occurring substances have demonstrated to have anti-carcinogenic activity. Their potential effect to inhibit cancer has been shown in vivo and in vitro studies. In this review, we present the multiple effects of CLA isomers on cancer development such as anti-tumor efficiency, anti-mutagenic and anti-oxidant activity. Although the majority of the studies in vivo and in vitro summarized in this review have demonstrated beneficial effects of CLA on the proliferation and apoptosis of tumor cells, further experimental work is needed to estimate the true value of CLA as a real anti-cancer agent.

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Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint

Nature Communications ◽

10.1038/s41467-021-22967-7 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Nathalie M. Schmidt ◽

Peter A. C. Wing ◽

Mariana O. Diniz ◽

Laura J. Pallett ◽

Leo Swadling ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Human Liver ◽

Lipid Droplets ◽

Ex Vivo ◽

Functional Cure ◽

Carcinogenic Activity ◽

Attractive Therapeutic Target ◽

Tcr Signalling

AbstractDetermining divergent metabolic requirements of T cells, and the viruses and tumours they fail to combat, could provide new therapeutic checkpoints. Inhibition of acyl-CoA:cholesterol acyltransferase (ACAT) has direct anti-carcinogenic activity. Here, we show that ACAT inhibition has antiviral activity against hepatitis B (HBV), as well as boosting protective anti-HBV and anti-hepatocellular carcinoma (HCC) T cells. ACAT inhibition reduces CD8+ T cell neutral lipid droplets and promotes lipid microdomains, enhancing TCR signalling and TCR-independent bioenergetics. Dysfunctional HBV- and HCC-specific T cells are rescued by ACAT inhibitors directly ex vivo from human liver and tumour tissue respectively, including tissue-resident responses. ACAT inhibition enhances in vitro responsiveness of HBV-specific CD8+ T cells to PD-1 blockade and increases the functional avidity of TCR-gene-modified T cells. Finally, ACAT regulates HBV particle genesis in vitro, with inhibitors reducing both virions and subviral particles. Thus, ACAT inhibition provides a paradigm of a metabolic checkpoint able to constrain tumours and viruses but rescue exhausted T cells, rendering it an attractive therapeutic target for the functional cure of HBV and HBV-related HCC.

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Carcinogenic Activity of Cigarette Smoke Condensate

JAMA ◽

10.1001/jama.1962.03050340006002 ◽

1962 ◽

Vol 181 (8) ◽

pp. 668 ◽

Cited By ~ 7

Author(s):

Fred G. Bock

Keyword(s):

Cigarette Smoke ◽

Cigarette Smoke Condensate ◽

Carcinogenic Activity

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The production of cancer by pure hydrocarbons. V

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1940.0046 ◽

1940 ◽

Vol 129 (857) ◽

pp. 439-467 ◽

Cited By ~ 43

Keyword(s):

Molecular Structure ◽

Carcinogenic Activity ◽

Carcinogenic Action

Tests for carcinogenic activity have been carried out with about seventy compounds, mostly new substances specially synthesized for the purpose and related to known carcinogenic compounds. The results support the view that there is a definite association between molecular structure and carcinogenic action; thus in the 3:4-benzphenanthrene series, which has not hitherto been investigated extensively, positions 1 and 2 seem to be the favourable points for substitution. The capacity to produce epithelioma does not always run parallel with the capacity to produce sarcoma. Some preliminary observations are given upon the occurrence of multiple tumours in animals receiving some classes of these compounds; this subject requires much further investigation with animals in which the spontaneous incidence of such tumours is known.

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Mouse Skin Bioassay for Chemical Carcinogens

Journal of the American College of Toxicology ◽

10.3109/10915818209013134 ◽

1982 ◽

Vol 1 (1) ◽

pp. 47-82 ◽

Cited By ~ 18

Author(s):

Michael A. Pereira

Keyword(s):

Aromatic Hydrocarbons ◽

Environmental Samples ◽

Alkylating Agents ◽

Mouse Skin ◽

Test Substance ◽

Review Of The Literature ◽

Carcinogenic Activity ◽

Tier Ii ◽

Direct Acting ◽

Halogenated Methanes

The mouse skin initiation/promotion bioassay is one of the proposed bioassays of the Carcinogenesis Testing Matrix for tier II (Bull and Pereira, 1980). A review of the literature indicated that 544 chemicals and substances have been examined by application to mouse skin for carcinogenic activity. Poly-cyclic aromatic hydrocarbons, direct acting alkylating agents, and environmental samples of complex mixtures and subtractions of them that include condensates of automobile exhaust and cigarette smoke have been demonstrated to be carcinogenic by the mouse skin bioassay. Chemical classes of carcinogens that have not been demonstrated to contain initiation and carcinogens in mouse skin include azoxy, diazo, halogenated methanes, hydrazine, inorganics, steroids, and sulfonates. The mouse skin assay can be modified so mat the test substance is administered systemically i.e., oral and intraperitoneal and the promoter applied topically. This modification has the potential of increasing the number of chemical classes detected in the mouse skin initiation/promotion bioassay.

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GENOTOXIC AND CARCINOGENIC STUDIES OF NORGESTREL IN DROSOPHILA MELANOGASTER

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i10.27374 ◽

2018 ◽

Vol 11 (10) ◽

pp. 372

Author(s):

Abou-eisha A ◽

Adel E El-din

Keyword(s):

Somatic Mutation ◽

Cellular Proliferation ◽

Research Work ◽

The Body ◽

The Other ◽

Direct Stimulation ◽

Carcinogenic Activity ◽

Genetic Examination ◽

First Time

Objective: The aim of this study was to investigate, for the first time, the possible in vivo genotoxic and carcinogenic activity associated with exposure to norgestrel (NGT) drug through employing the very recently established and adjusted genotoxic and tumorigenic methods in Drosophila melanogaster.Methods: Two in vivo genotoxic test systems were used; one detects the somatic mutation and recombination effects (somatic mutation and recombination test [SMART] wing-spot test) and the other detects the primary DNA damage (the comet test) in the body cells of D. melanogaster. On the other hand, the warts (wts)-based SMART assay is a vital genetic examination in Drosophila used to identify and characterize cancer potential of compounds.Results: Four experimental doses of NGT were used (ranging from 0.24 μM to 16 μM). NGT was found to be non-genotoxic at all tested concentrations even at the highest dose level 16 μM and failed to increase the frequency of tumors in the somatic cells of D. melanogaster.Conclusion: Our results strengthen the hypothesis that steroidal drugs might act through a non-genotoxic carcinogen mechanism where the carcinogenic properties occur by direct stimulation of cellular proliferation through a steroid receptor-mediated mechanism. In addition, the results obtained in this research work may contribute to highlighting the importance of NGT as a potent neuroprotective antioxidant drug.

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