Interventional study of high dose folic acid in gastric carcinogenesis in beagles.
BACKGROUND
A decrease in folic acid and subsequent DNA hypomethylation may be involved in gastric carcinogenesis. Epidemiological and nutritional studies have indicated that folate status modulates the risk of developing cancers.


OBJECTIVE
To investigate whether folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by N-ethyl-N-nitrosoguanidine (ENNG) in beagles.


METHODS
Sixteen male beagles were randomly divided into two groups: folic acid treated group and control group. In both groups beagles were fed ENNG 75 mg per day for eight months and in the treated group 20 mg folic acid was given to beagles for 15 months. Gastroscopy and biopsies were performed before and every 2-3 months after administration of ENNG until the end of the experiment. Histopathological lesions were diagnosed with regard to the criteria for human gastric mucosal biopsies. Serum and gastric mucosal tissue folic acid concentrations were measured.


RESULTS
In the control group, all beagles developed gastric cancer (8/8) compared with only 3/8 in the folic acid treated group (p<0.05). Moreover, serum and gastric mucosal tissue folic acid concentrations were markedly elevated 15 months after folic acid administration. The difference was statistically significant between the two groups (p<0.05).


CONCLUSIONS
Our results indicate that high dose folic acid plays an important role in the chemoprevention of gastric carcinogenesis induced by a chemical carcinogen ENNG in beagles.
Xiao
S D
SD
Shanghai Institute of Digestive Disease, Shanghai Second Medical University, Renji Hospital, Shanghai 200001, P R China. sdxiao@guomai.sh.cn
Meng
X J
XJ
Shi
Y
Y
Hu
Y B
YB
Zhu
S S
SS
Wang
C W
CW
D000818:Animals; D002273:Carcinogens; D004285:Dogs; D005492:Folic Acid / Q000032:analysis / Q000627:therapeutic use*; D005753:Gastric Mucosa / Q000737:chemistry / Q000473:pathology; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000031:analogs & derivatives*; D011863:Radioimmunoassay; D011933:Reagent Kits, Diagnostic; D013053:Spectrophotometry; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016896:Treatment Outcome
D002273:Carcinogens; D011933:Reagent Kits, Diagnostic; D008769:Methylnitronitrosoguanidine; C013525:ENNG; D005492:Folic Acid