Methods to detect non-genotoxic carcinogens using flatworms

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.

1 . A method for determining risk that a compound is a genotoxic carcinogen, the method comprising:
 exposing a flatworm to the compound for a period of time,   measuring the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, within said flatworm after exposure to said compound, wherein said number of adult pluripotent stem cells excluding gonadal phosphorylated H3-positive cells is quantified by a phosphorylated histone H3 immunoassay,   comparing the number of adult pluripotent stem cells within the flatworm after exposure to the compound to a reference value, wherein the reference value is determined by measuring with a phosphorylated histone H3 immunoassay the number of adult pluripotent stem cells, excluding gonadal phosphorylated H3-positive cells, within a flatworm after exposure to a non-genotoxic carcinogen, and   determining whether the compound has a risk of being a genotoxic carcinogen, wherein when said number of adult pluripotent stem cells excluding gonadal phosphorylated H3-positive cells, is less than said reference value, the compound has a higher risk of being a genotoxic carcinogen.   
     
     
         2 . The method according to  claim 1 , wherein said period of time is 2 weeks. 
     
     
         3 .- 6 . (canceled) 
     
     
         7 . The method according to  claim 1 , wherein said flatworm is  Macrostomum lignano  or  Schmidtea mediterranea.    
     
     
         8 .- 15 . (canceled)