Enzyme polymorphisms influencing the metabolism of heterocyclic aromatic amines.
Heterocyclic aromatic amines are dietary carcinogens possibly involved in human carcinogenesis, DNA-adduct formation being an obligatory step in this multistage process. Heterocyclic amine binding to DNA largely depends on the balance between metabolic activation and detoxification pathways and DNA repair efficiency. Several genes coding for metabolic enzymes are polymorphic, which affects gene expression and/or enzyme activity. This paper briefly reviews the effect of polymorphisms of activating/detoxifying enzymes on the metabolism of heterocyclic amines. Despite some epidemiological evidence of an association between genetic polymorphisms and susceptibility to cancer possibly resulting from dietary exposure to heterocyclic aromatic amines (HA), the genetic polymorphisms had only slight effects on biomarker levels, suggesting the existence of further unknown factors.
Airoldi
Luisa
L
Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, Milan 20157, Italy. airoldi@marionegri.it
Magagnotti
Cinzia
C
Pastorelli
Roberta
R
Fanelli
Roberto
R
D000588:Amines / Q000378:metabolism*; D000818:Animals; D004798:Enzymes / Q000235:genetics*; D006571:Heterocyclic Compounds / Q000378:metabolism*; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology; D011110:Polymorphism, Genetic
D000588:Amines; D004798:Enzymes; D006571:Heterocyclic Compounds