Direct involvement of human gastric mucosa in the activation of alimentary pro-carcinogens.
Exposure to N-nitroso-compounds and aromatic amines, xenobiotics which require an activation in order to exert their genotoxic potential, is causally associated with gastric cancer. We evaluated the capacity of microsome-containing fractions from human gastric mucosa to activate two model carcinogenic compounds. A 9,000 x g supernatant (S9) was obtained from gastric mucosal specimens and, for comparison, from human liver and aroclor-induced and non induced rat liver. The capacity of the S9 to activate N-nitrosopyrrolidine (NPY) and 2-aminofluorene (2AF) to mutagenic metabolites was tested in the Ames/Salmonella reversion assay, while dimethylnitrosamine (DMN) and aminopyrine (AP) demethylation activities were spectrophotometrically evaluated by using an enzymatic assay of the amount of formaldehyde released following the enzymatic demethylation of the corresponding substrates. Results indicate that human gastric S9 fractions may activate 2AF to a genotoxic derivative and are characterized by DMN and AP demethylase activities higher (p < 0.05) than those of human liver, when expressed in mg/protein (p < 0.05). Although the parameters evaluated can only be considered as a partial measure of the general activating capacity toward dietary and environmental procarcinogens, these results suggest that human gastric mucosa may be directly involved in the metabolic activation of these compounds to mutagenic/carcinogenic species.
Farinati
F
F
Cattedra Malattie Apparato Digerente Istituto di Medicina Interna, Universita Degli Studi di Padova, Italy.
Zordan
M
M
Cardin
R
R
Levis
A G
AG
Nitti
D
D
Lise
M
M
Valiante
F
F
Naccarato
R
R
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D002273:Carcinogens / Q000493:pharmacokinetics*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005449:Fluorenes / Q000493:pharmacokinetics; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D009153:Mutagens / Q000493:pharmacokinetics; D009242:N-Nitrosopyrrolidine / Q000493:pharmacokinetics; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011355:Prodrugs / Q000493:pharmacokinetics; D051381:Rats; D014020:Tissue Extracts / Q000378:metabolism
D001140:Aroclors; D002273:Carcinogens; D005449:Fluorenes; D009153:Mutagens; D011355:Prodrugs; D014020:Tissue Extracts; C012177:2-aminofluorene; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase; D009242:N-Nitrosopyrrolidine