Premium
DNA fragmentation in mouse gastric epithelial cells by precarcinogens, ultimate carcinogens and nitrosation products: An indicator for the determination of organotropy and metabolic activation
Author(s) -
Koropatnick D. J.,
Stich H. F.
Publication year - 1976
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910170612
Subject(s) - carcinogen , fragmentation (computing) , stomach , nitrosation , dna , dna fragmentation , nitrosamine , chemistry , gastrointestinal tract , biochemistry , microbiology and biotechnology , biology , apoptosis , ecology , programmed cell death
Abstract The feasibility of using alkaline sucrose gradient analysis of the digestive tract tissue of mice to uncover the carcinogenic capacity of organotropic compounds was examined. Young Swiss mice were injected with 3 H‐TdR to label the DNA of the epithelial cells of the digestive tract. They were force‐fed carcinogenic and non‐carcinogenic chemicals 30 h later. Tissue samples were taken 4 h post‐treatment and hydrolized on top of the aklaline sucrose gradient. Shifts in sedimentation profiles indicated that: (1) the carcinogen 4‐nitroquinoline 1‐oxide (4NQO) 1 and 6‐methyl 4NQO cause DNA fragmentation in the epithelial cells of oesophagus, cardiac and pyloric stomach while the non‐carcinogen 6NQO lacks this capacity; (2) the ultimate carcinogen N‐acetoxy‐2AAF caused DNA fragmentation in oesophagus and stomach cells whereas precarcinogen 2‐AAF exerted no detectable effect; (3) only carcinogenic nitrosation products of MG damaged the DNA; and (4) the precarcinogens 2‐AAF and DMN elicited DNA fragmentation in their main target organ, the liver, but had no effect on the epithelial cells of oesophagus and stomach. The results suggest that the application of the sucrose gradient technique to the epithelial cells of oesophagus, stomach and liver of pre‐labelled ( 3 H‐TdR) and force‐fed young mice incorporates the advantages of in vitro short‐term bioassays with the completeness of tests using whole mammals.