Table 4.
Summary of the ALD-induced hepatocarcinogenesis protocols in rodents.
| Model | Procedure | Animal (Species, Strain, Age) | Timepoints and Incidence of Lesions | References |
|---|---|---|---|---|
| Ethanol | Liquid low (1%, w/w) or high (3%, w/w) ethanol diet for ~100–110 weeks | Juvenile to adult (6–7 weeks) Sprague-Dawley rats (male and female) | Neoplastic lesions: 2% at weeks ~100–110 (for both doses and sexes) | [178] |
| Ethanol in drinking water 2.5% or 5% (v/v) for 104 weeks | Juvenile (4 weeks) B6C3F1 mice (male) | Neoplastic lesions: 34% (2.5%) and 52% (5%) at week 108 Adenomas: 25.5% (2.5%) and 39.6% (5%) at week 108 |
[179] | |
| MeIQx and Ethanol | MeIQx: 200 mg/kg diet for 8 weeks Ethanol in drinking water 10 or 20% (v/v) for 16 weeks |
Juvenile (3 weeks) F344/DuCrj rats (male) | Adenomas: ~80% (10%) or ~100% (20%) at week 27 Carcinomas: ~20% (10%) or ~50% (20%) at week 27 |
[183] |
| Resistant hepatocyte and Ethanol | DEN: Single i.p. 200 mg/kg b.w.,at week 6 2-AAF: 200 mg/kg in diet for 3 weeks PH: at week 9 Ethanol in drinking water 5% (v/v) for 5 or 15 weeks |
Juvenile (4 weeks) Wistar rats (male) | Preneoplastic foci: 63%–100% at week, 18 44%–100% at week 28 * Adenomas: 75% at week 18, 94% at week 28 * Carcinomas: 0% at week 18, 0% at week 28 * |
[184] |
| DEN and Ethanol | DEN: Single i.p. 200 mg/kg b.w., at week 9 Ethanol in drinking water 5% (v/v) for 16 weeks |
Adult (9 weeks) WT rats | Adenomas: 8% at week 25 Carcinomas: 0% at week 25 |
[182] |
| Adult (9 weeks) Cx32 dominant-negative transgenic rats | Adenomas: 25% at week 25 Carcinomas: 25% at week 25 |
|||
| DEN: Single i.p.10 mg/kg b.w., at week 2 Lieber-Decarli diet (4.9% of ethanol, v/v) for 16 weeks |
Infant (2 weeks) C57BL/6 mice (male and female) | Eosinophilic foci: 53% at week 23 Adenomas: 60% at week 23 * Carcinomas: 13% at week 23 * |
[185] | |
| DEN: Single i.p. 1 mg/kg b.w. at weeks 3–4 Ethanol in drinking water 5% (v/v) for 3 days, followed by 10% (v/v) for 3 days and 10/20% (v/v) (alternate days) for 8 weeks, during weeks 16 to 24 or 40 to 48 |
Juvenile (3–4 weeks) B6C3 mice (male) | Neoplastic lesions: 97.5% at week 48 * | [186] | |
| DEN, Ethanol and HF | DEN: Single i.p. 25 mg/kg b.w. at weeks 2 Liquid ethanol diet (gradually increased from 1% to 2% and 3% (v/v, throughout 3 weeks), and maintained at 3.5% (v/v)) for 18 or 24 weeks. |
Infant (2 weeks) C57BL/6 mice (male) | Carcinomas: ~20% at week 18; ~70% at week 24 | [187] |
* not statistically different from DEN-only control mice. 2-AAF: 2-Acetylaminefluorene; ALD: alcoholic liver disease; b.wt.: body weight; Cx32: connexin 32; i.p.: intraperitoneal. DEN: diethylnitrosamine; MeIQx: 2-amino-3, 8-dimethylimidazo 4,5-f]quinoxaline; PH: patial hepatectomy.