World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 8, Number 4, August 2017, pages 97-104

4-Nitroquinoline 1-Oxide-Induced Tongue and Esophagus Carcinogenesis in Obese and Diabetic TSOD Mice

Figure 1. Histopathology of tongue proliferative lesions developed in male TSOD mice treated with 20 ppm 4-NQO in drinking water: (a) moderate dysplasia; (b) squamous cell papilloma; (c) carcinoma in situ; (d) invasive squamous cell carcinoma. Hematoxylin and eosin stain, bar = 100 µm.

Figure 2. Histopathology of esophageal proliferative lesions in male TSOD mice treated with 20 ppm 4-NQO in drinking water: (a) moderate dysplasia; (b) squamous cell papilloma; (c) carcinoma in situ; (d) invasive squamous cell carcinoma. Hematoxylin and eosin stain, bar = 100 µm.

Figure 3. Measures of esophageal cytokines and chemokines in a short-term experiment using 16 male TSOD and 16 male TSNO mice given tap water with or without 20 ppm 4-NQO for 8 weeks. At 8 weeks after the start of the experiment: (a) TNF-α, (b) IL-1β, (c) IFN-γ, (d) IL-6, (e) IL-17, (f) CXCL1/KC, (g) CCL3/MIP-1α, and (h) CXCL2/MIP-2.

**Table 1.** Body, Liver and Visceral Fat Weights
Treatment	TSOD mice	TSNO mice
aMean ± SD. ^bVisceral fat includes epididymal, mesenteric, retroperitoneal and perinephric fats.
Body weight (g)
Initial	35.1 ± 1.2a	35.4 ± 2.0	23.6 ± 2.2	25.1 ± 1.7
Final	63.3 ± 2.2	64.5 ± 2.7	43.5 ± 2.1	45.4 ± 2.1
Liver weight (g)	1.64 ± 0.12	1.59 ± 0.20	1.48 ± 0.17	1.52 ± 0.14
Visceral fat weight^b (g)	5.52 ± 0.21	5.62 ± 0.19	1.39 ± 0.17	1.59 ± 0.21

Table 1. Body, Liver and Visceral Fat Weights

Treatment

TSOD mice

TSNO mice

4-NQO (n = 20)

None (n = 8)

4-NQO (n = 20)

None (n = 8)

aMean ± SD. ^bVisceral fat includes epididymal, mesenteric, retroperitoneal and perinephric fats.

Body weight (g)

Initial

35.1 ± 1.2a

35.4 ± 2.0

23.6 ± 2.2

25.1 ± 1.7

Final

63.3 ± 2.2

64.5 ± 2.7

43.5 ± 2.1

45.4 ± 2.1

Liver weight (g)

1.64 ± 0.12

1.59 ± 0.20

1.48 ± 0.17

1.52 ± 0.14

Visceral fat weight^b (g)

5.52 ± 0.21

5.62 ± 0.19

1.39 ± 0.17

1.59 ± 0.21

**Table 2.** Clinical Chemistry
	TSOD mice	TSNO mice
^aMean ± SD.
Glucose (mg/dL)	171 ± 29^a	135 ± 19	90 ± 21	102 ± 13
Triglyceride (mg/dL)	233 ± 39	113 ± 61	33.6 ± 4.6	16.4 ± 3.5
Total cholesterol (mg/dL)	227 ± 22	183 ± 46	137 ± 13	121 ± 12
HDL-cholesterol (mg/dL)	116 ± 20	107 ± 13	160 ± 16	139 ± 20
LDL-cholesterol (mg/dL)	37.8 ± 9.1	24.0 ± 11.2	12.2 ± 1.3	18.8 ± 4.7

Table 2. Clinical Chemistry

TSOD mice

TSNO mice

4-NQO

None

4-NQO

None

^aMean ± SD.

Glucose (mg/dL)

171 ± 29^a

135 ± 19

90 ± 21

102 ± 13

Triglyceride (mg/dL)

233 ± 39

113 ± 61

33.6 ± 4.6

16.4 ± 3.5

Total cholesterol (mg/dL)

227 ± 22

183 ± 46

137 ± 13

121 ± 12

HDL-cholesterol (mg/dL)

116 ± 20

107 ± 13

160 ± 16

139 ± 20

LDL-cholesterol (mg/dL)

37.8 ± 9.1

24.0 ± 11.2

12.2 ± 1.3

18.8 ± 4.7

**Table 3.** Tongue Proliferative Lesions
Lesions	TSOD mice treated with 4-NQO	TSNO mice treated with 4-NQO
^aMean ± SD.
Dysplasia	100	4.80 ± 1.44^a	100	3.95 ± 1.47
Papilloma	15	0.20 ± 0.52	10	0.10 ± 0.31
Squamous cell carcinoma	20	0.30 ± 0.66	25	0.30 ± 0.57
Total tumors	30	0.50 ± 0.89	30	0.40 ± 0.68

Table 3. Tongue Proliferative Lesions

Lesions

TSOD mice treated with 4-NQO

TSNO mice treated with 4-NQO

Incidence (%)

Multiplicity (no. of lesions/mouse)

Incidence (%)

Multiplicity (no. of lesions/mouse)

^aMean ± SD.

Dysplasia

100

4.80 ± 1.44^a

100

3.95 ± 1.47

Papilloma

0.20 ± 0.52

0.10 ± 0.31

Squamous cell carcinoma

0.30 ± 0.66

0.30 ± 0.57

Total tumors

0.50 ± 0.89

0.40 ± 0.68

**Table 4.** Esophageal Proliferative Lesions
Lesions	TSOD mice treated with 4-NQO	TSNO mice treated with 4-NQO
^aMean ± SD. ^b-dSignificantly different from the values of the TSNO mice treated with 4-NQO (^bP < 0.05, ^cP < 0.001, and ^dP < 0.01).
Dysplasia	100	6.55 ± 1.73^a	100	6.75 ± 3.32
Papilloma	60^b	1.5 0 ± 1.70^b	30	0.60 ± 1.14
Squamous cell carcinoma	50^c	0.75 ± 0.91	0	0
Total tumors	70	2.25 ± 2.29^d	30	0.60 ± 1.14

Table 4. Esophageal Proliferative Lesions

Lesions

TSOD mice treated with 4-NQO

TSNO mice treated with 4-NQO

Incidence (%)

Multiplicity (no. of lesions/mouse)

Incidence (%)

Multiplicity (no. of lesions/mouse)

^aMean ± SD. ^b-dSignificantly different from the values of the TSNO mice treated with 4-NQO (^bP < 0.05, ^cP < 0.001, and ^dP < 0.01).

Dysplasia

100

6.55 ± 1.73^a

100

6.75 ± 3.32

Papilloma

60^b

1.5 0 ± 1.70^b

0.60 ± 1.14

Squamous cell carcinoma

50^c

0.75 ± 0.91

Total tumors

2.25 ± 2.29^d

0.60 ± 1.14