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US 10,197,556 B2Granted
Methods to detect non-genotoxic carcinogens using flatworms
AssigneesUniversiteit Gent, Universiteit Hasselt
InventorsKaren Smeets, An-Sofie Stevens, Michelle Plusquin, Tom Artois, Maxime Willems, Jean Paul Remon
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Abstract
This disclosure relates to predicting the carcinogenicity of compounds. More in particular, this application discloses methods to detect whether a compound is a non-genotoxic carcinogen and methods to discriminate between genotoxic and non-genotoxic carcinogens based on in vivo stem cell proliferation patterns in flatworms.
Claims7
A method for determining whether a compound is a genotoxic carcinogen, the method comprising:
- cutting a flatworm transversally in order to create at least one regenerating flatworm,
- exposing a regenerating flatworm therefrom to the compound for a period of time and at a concentration that triggers phenotypic effects in regenerating flatworms,
- determining the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, within said regenerating flatworm after exposure to the compound, wherein the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells is determined with a phosphorylated histone H3 immunoassay, and
- comparing the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, within the regenerating flatworm after exposure to the compound to the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, within a regenerating flatworm obtained by a similar exposure to a non-carcinogenic, control compound,
- so as to classify the compound as a genotoxic carcinogen when the determined number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, is significantly lower than the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, within a regenerating flatworm after the similar exposure to the non-carcinogenic, control compound.
2 more elements
A method of detecting whether a compound is a non-genotoxic carcinogen, the method comprising:
- cutting a flatworm transversally in order to create at least one regenerating flatworm,
- exposing the regenerating flatworm to the compound for at least three (3) days,
- determining the number of adult pluripotent stem cells, execluding gonadal phosphorylated H3-positive cells, within said regenerating flatworm after said exposure to the compound, wherein the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, is determined with a phosphorylated histone H3 immunoassay, and
- comparing the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, within the regenerating flatworm after exposure to the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, within a regenerating flatworm obtained by a similar exposure to a non-carcinogenic, control compound, so as to classify the compound,
- wherein the compound is classified as a non-genotoxic carcinogenic when there is a concentration-dependent increase in the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, at day 3 post-exposure,
- wherein the compound is classified as a genotoxic carcinogenic when there is a concentration-dependent decrease in the number of adult pluripotent stem cells, excluding gonadal phosphorylate H3-positive cells, at day 3 post-exposure, and
- wherein the compound is classified as non-carcinogenic when there is no concentration-dependent change in the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, at day 3 post-exposure.
4 more elements
A method for determining whether a compound is a genotoxic carcinogen, the method comprising:
- cutting a flatworm transversallv in order to create at least one regenerating flatworm,
- exposing a first regenerating flatworm to a test compound at a concentration and for a period of time that is at least three (3) days;
- determining the number of adult pluripotent stem cells, exeluding gonadal phosphorylated H3-positive cells, within the first regenerating flatworm after the period of time, wherein the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, is determined with a phosphorylated histone H3 immunoassay;
- exposing a second regenerating flatworm to a non-carcinogenic, control compound for the period of time that the first regenerating flatworm was exposed to the test compound;
- and
- determining the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, within the second regenerating flatworm after treatment with the non-carcinogenic, control compound with a phosphorylated histone H3 immunoassay,
- wherein the test compound is determined to be a genotoxic carcinogen when the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, determined in the first regenerating flatworm is significantly less than the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, determined in the second regenerating flatworm.
4 more elements
Dependencies are inferred from the claim text.