Table 2.

Summary of some of the chemically induced hepatocarcinogenesis protocols in rats and mice strains.

Model	Procedure	Animal (Species, Strain, Age)	Timepoints and Incidence of Lesions	References
DEN	Single i.p., 90 mg/kg b.w.	Juvenile (5 weeks) C3H/He, DBA/2 and C57BL/6 mice (male)	-Adenomas: 0–20% at week 24, 10–50% at 36, and 20–50% at weeks 36–52 (strain-dependent) -Carcinomas: 0% at week 24, 0% at 36, and 0–40% at weeks 36–52 (strain-dependent)	[41]
	Multiple i.p. 1.5 or 3 mg/kg b.w. for 1 week (4×/week)	Juvenile (6 weeks) B6C3F1 and C3AF1 mice (male)	-Adenomas: 3–8% at weeks 100–120 (strain- and dose-dependent) -Carcinomas: 16–22% at weeks 100–120 (strain- and dose-dependent)	[42]
	Drinking water 15 mg/L for 3 weeks	Juvenile (4 weeks) B6C3F1 mice (male)	-Adenomas: 100% at week 24	[43]
	Multiple i.p. 25, 50, or 75 mg/kg b.w., for 4 or 8 weeks (1×/week)	Juvenile (4 weeks) C57BL/6 mice (male)	-Preneoplastic foci: 44–100% at week 33 (dose-dependent) -Adenomas: 0–33% at week 33 (dose-dependent) -Carcinomas: 0% at week 33	[44]
	Single i.p. 2.5, 10, 25 or 50 mg/kg b.w.	Infant (2 weeks) BALB/c mice (male)	-Adenomas: 7–87% at week 24 and 10–100% at week 40 (dose-dependent) -Carcinomas: 5–10% at both weeks at week 40 (dose-dependent)	-[45]
	Single i.p. 5 mg/kg b.w.	Infant (2 weeks) C3H/HeJ, B6C3F1 and C57BL mice (male)	-Adenomas: 90–100% at week 28 (strain-dependent)	[46]
	Single i.p. 1 mg/kg b.w.	Infant (2 weeks) C3H/HeJ, B6C3F1 and C57BL mice (male)	-Preneoplastic foci: 25–56% at week 22 and 46–100% at week 48 (strain-dependent) -Adenomas + Carcinomas: 25–67% at week 22 and 77–100% at week 48 (strain-dependent)	[47]
	Single i.p. 1 mg/kg b.w.	Infant (2 weeks) B6C3F1 mice (male)	-Preneoplastic foci: 75% at week 17 and 100% at week 22 -Adenomas: 0% at week 17 and 12.5% at week 22 -Carcinomas: 0% at both weeks 17 and 22	[48]
	Multiple i.p. 20 (1 dose), 30 (1 dose) and 50 mg/kg (6 doses) b.w., for 8 weeks (1×/week)	Infant (2 weeks) C57BL/6 mice (male and female)	-Adenomas + Carcinomas: 100% at week 24 -Obs.: Liver Fibrosis	[49]
	Gavage 80 mg/kg b.w. (weeks ~6–7)	Adult (~6–7 weeks) Sprague-Dawley rats (male)	-Carcinomas: ~5–20% at week 48 and 70	[50]
	Single i.p., 200 mg/kg b.w. (week 6)	Juvenile (4 weeks) F344 rats (male)	-Preneoplastic foci: 100% at week 42 -Adenomas: 7% at week 42 -Carcinomas: 0% at week 42	[51]
	Multiple i.p. 70 mg/kg b.w., for 10 weeks (1×/week)	Adult (6 weeks) Sprague-Dawley rats (male)	-Carcinomas: 100% at week 20 -Obs.: Liver Cirrhosis	[52]
	Multiple i.p. 30 mg/kg b.w. for 11 weeks (2×/week)	Juvenile (4–5 weeks) Sprague-Dawley rats (male)		[53]
	Multiple gavage 70 mg/kg b.w. for 14 weeks (1×/week)	Juvenile (4–5 weeks) Wistar rats (male)	-Carcinomas: 80% at week 30 and 100% at week 34 -Lung metastasis: 20% at week 34 -Obs.: Liver Cirrhosis	[54]
DEN and CCl4	-DEN: Single i.p. 10 mg/kg b.w. (week 2) -CCl4: Multiple i.p. 0.25 to 1.50 mg/kg b.w. for 8 weeks (3×/week)	Infant (2 weeks) C3H/HeJ mice (male)	-Preneoplastic foci: 100% at week 17 -Adenomas: 100% at week 17 -Carcinomas: 12.5% at weeks 17	[55]
	-DEN: Single i.p. 10 mg/kg b.w. (week 2) -CCl4: Multiple i.p. 0.2 mL/kg b.w. for 9 or 14 weeks (2×/week)	Infant (2 weeks) B6C3F1 mice (male)	-Preneoplastic foci: 100% at week 17 and 25% at week 22 -Adenomas: 37.5% at week 17 and 100% at week 22 -Carcinomas: 20% at week 17 and 50% at week 22	[48]
	-DEN: Single i.p. 200 mg/kg b.w. (week 4–5) -CCl4: Multiple gavage 0.5 mL/kg b.w. for 6 weeks (3×/week)	Juvenile (4–5 weeks) F344 rats (male)	-Preneoplastic foci: ~81% at week 16 -Adenomas: 100% at week 16 -Carcinomas: 73% at week 16	[56]
CCl4	-CCl4: Multiple i.p. 0.2 mL/kg b.w. for 9 or 14 weeks (2×/week)	Infant (2 weeks) B6C3F1 mice (male)	-Preneoplastic foci: 0% at week 17 and 12.5% at week 22 -Adenomas: 0% at week 17 and 12.5% at week 22 -Carcinomas: 0% at week 17 and 25% at week 22	[48]
DEN and TAA	-DEN: Multiple i.p. 20 (1 dose), 30 (1 dose) and 50 mg/kg (6 doses) b.w., for 8 weeks (1×/week) -TAA: Multiple i.p. 300 mg/kg b.w., for 4 or 8 weeks (2×/week)	Infant (2 weeks) C57BL/6 mice (male and female)	-Adenomas + Carcinomas: 100% at week 24 (for both doses)	[49]
	-DEN: Single i.p. 200 mg/kg b.w. (week 6) -TAA: Multiple i.p. 200 mg/kg b.w. for 24 weeks (2×/week) (cycles of 3 weeks of administration and 1 week of rest)	Adult (6 weeks) Wistar rats (male)	-Preneoplastic foci: 100% at week 26 -Adenomas: 30% at week 26 -Carcinomas: 10% at week 26	[57]
DEN, TAA and PB	-DEN: Single i.p. 200 mg/kg b.w. (week 6) -PB: 0.05% diet for 1 week -TAA: Drinking water 0.03% for 9, 10, 20 or 30 weeks	Adult (6 weeks) F344 rats (male)	-Adenomas: 0% at week 9, 16.7% at week 20, 100% at weeks 30 and 40 -Carcinomas: 0% at weeks 9 and 20, 25% at week 30, and 75% at week 40	[58]
DEN and PB	-DEN: Single i.p., 90 mg/kg b.w. (week 5) -PB: Drinking water 0.05% (week 7) for 17, 31 or 45 weeks	Juvenile (5 weeks) C3H/He, DBA/2 and C57BL/6 mice (male)	-Adenomas: 10–90% at week 24, 50–60% at 36, and 0–30% at weeks 36–52 (strain-dependent) -Carcinomas: 0% at week 24, 0–40% at 36, and 0–100% at weeks 36–52 (strain-dependent)	[41]
	-DEN: Gavage 80 mg/kg b.w. (weeks ~6–7) -PB: Drinking water 0.025, 0.05 or 0.1% (weeks ~7–8) for ~48 or ~70 weeks	Adult (~6–7 weeks) Sprague-Dawley rats (male)	-Carcinomas: ~5–20% at week 48 and 50–60% at week 70	[50]
	-DEN: Single i.p., 200 mg/kg b.w. (week 6) -PB: Drinking water 0.05% (week 7) for 36 weeks	Juvenile (4 weeks) F344 rats (male)	-Preneoplastic foci: 100% at week 42 -Adenomas: 64% at week 42 -Carcinomas: 50% at week 42	[51]
DEN, 2-AAF and PH	-DEN: Single i.p., 200 mg/kg b.w. (week 1) -2-AAF: diet 0.02% for 2 weeks (weeks 3 and 4) -PH: 67% (week 3)	Adult Fischer 344 rats (male)	-Carcinomas: 68–71% at week 32, 75% at week 40 -Metastasis: ~3–4% at week 32, ~4% at week 40	[59]

i.p. = intraperitoneal; b.w. = body weight. 2-AAF: 2-acetylaminofluorene; CCl₄: carbon tetrachloride; DEN: diethylnitrosamine; PB: phenobarbital; PH: partial hepatectomy; TAA: thioacetamide.