Helicobacter pylori-infected animal models are extremely suitable for the investigation of gastric carcinogenesis

Table 1 Duration of H pylori infection and number of point mutations in exon 5-8 of the p53 gene

Monkey	Durationof H pyloriinfection(yr)	Number of nucleotide(amino acid) substitutionsin p53				Atrophyscore1	Intensity of p53immunostaining2
		Ex 5	Ex 6	Ex 7	Ex 8		-
A	1.5	0(0)	2 (1)	0 (0)	1 (1)	2	-
B	2	4 (0)	2 (2)	5 (4)	4 (3)	3	+
C	3	4 (2)	1 (0)	2 (2)	2 (2)	4	+
D	3	2 (1)	1 (0)	1 (1)	4 (2)	5	+
E	3.5	5 (2)	2 (1)	5 (4)	6 (4)	4
F	4.5	5 (1)	3 (1)	4 (3)	5 (4)	6	-
G	5	4 (1)	3 (1)	2 (1)	8 (6)	8	+
H	7.5	8 (5)	2 (1)	5 (4)	8 (4)	12	++

¹, The atrophy score was calculated as the sum of the histological evaluations of five gastric specimens according to Updated Sydney System.

², The intensity of p53 immunostaining was classified into four grades: -, no staining; +, mild staining; ++, moderate staining; +++, intense staining.

Table 2 Gastric carcinogenesis in Helicobacter pylori-infected Mongolian gerbils

Author	Year	Strain	Study design (ppm)	Incidence ofcancer (%)	Duration ofexperiment (wk)
Sugiyama et al.	1998	ATCC43504	HP→MNU (10) HP alone MNU (30) → HP MNU alone	7/19 (36.8) 0/20 (0) 6/18 (33.3) 0/74 (0)	40 40 40 40
Tokieda et al.	1999	ATCC43504	HP → MNNG (50) persistent HP positive HP eradicated Br → MNNG (50)	5/17 (29.4) 5/8 (62.5) 0/9 (0) 3/22 (13.6)	52 52 52 50
Shimizu et al.	1999	ATCC43504	MNNG (300) → HP MNNG (300) → Br MNNG (60) → HP MNNG (60) → Br HP → MNNG (100) Br → MNNG (100) HP → MNNG (20) Br → MNNG (20) HP alone	12/27 (44.4) 1/19 (5.3) 6/25 (24.0) 0/20 (0) 4/27 (14.8) 3/18 (16.7) 15/25 (60) 1/20 (5) 0/20 (0)	50 50 50 50 50 50 50 50 50

HP, Helicobacter pylori; MNU, N-methyl-N-nitrosourea; MNNG, N-methyl-N’-nitroso-N-nitrosoguanidine; Br, Brucella broth.

Table 3 Gastric carcinogenesis in Helicobacter pylori-infected Mongolian gerbils

Author	Year	Strain	cagA gene	Vacuolating	Incidence of	Duration of	Histological type of
				cytotoxin	cancer (%)	experiment (wk)	carcinoma
Watanabe et al.	1998	TN2GF41	+	+	10/27 (37)	62	Well differentiated
							adenocarinoma
Honda et al.	1998	ATCC435042	+	+	2/5 (40)	72	Well differentiated
							adenocarinoma
Hirayama et al.	1999	ATCC435042	+	+	1/56 (1.8)	64	Well differentiated
							adenocarinoma
Ogura et al.	2000	TN22	+	+	1/23 (4)	62	Well differentiated
							adenocarinoma
Zheng et al.	2004	ATCC435042	+	+	3/17 (18)	84	Well differentiated
		H pylori 1613	+	+			adenocarinoma

¹H pylori isolated from patient with gastric ulcer;

²Type of strains;

³H pylori isolated from patient with gastric adenocarcinoma.

Table 4 Gastric carcinogenesis in Helicobacter pylori-infected Mongolian gerbils

Histropathological findings	Mo
	6	12	18	24
Gastritis	5/5	4/4	5/5	10/10
Gastric ulcer	4/5	3/4	5/5	5/10
Atrophy	4/5	4/4	5/5	10/10
Intestinal metaplasia	2/5	3/4	5/5	10/10
Dysplasia	0/5	2/4	4/5	10/10
Gastric cancer	0/5	0/4	2/5	5/10
Gastric carcinoid	0/5	0/4	0/5	5/10

Data represent positive case/control Uninfected control. animals (n = 5 each) showed no abnormal findings.

Table 5 Relation between p53 and H pylori and gastric mucosal change (tentative opinion)

Condition	Human	Japanesemonkey	Mongoliangerbil
H pylori and p53	++	++	+1
overexpression (histology)
H pylori and p53 point mutation	++	++	-
H pylori and atrophic gastritis	++	++	++
H pylori and intestinal metaplasia	++	-	++
H pylori and gastric cancer	+2	-	++

¹The p53 overexpression was observed only in gastric cancer;

²Not proven by interventional study; ++, strong evidence; +, weak evidence; -, no evidence