Table 1. Effect of antidiabetic biguanides on spontaneous and induced carcinogenesis in rodents.
| Target organ | Sex | Species, strain | Carcinogenic agent | Drug | Doses | Route | Effect | References |
|---|---|---|---|---|---|---|---|---|
| Mammary gland | F | C3H/Sn mice | MMTV | PF | 2 mg/mouse | oral | ↓ | (9,10) |
| F | FVB/N mice | HER-2/neu | MF | 100 mg/kg | d.w. | ↓ | (29,43) | |
| F | SHR mice | spontaneous | MF | 100 mg/kg | d.w. | = | (44) | |
| F | LIO rats | DMBA | PF | 5 mg/rat | oral | ↓ | (6,8) | |
| F | LIO rats | DMBA | BF | 5 mg/rat | oral | ↓ | (15) | |
| F | LIO rats | NMU | PF | 1 mg/rat | oral | ↓ | (14) | |
| F | SD rats | NMU | MF | 5 mg/kg | oral | = | (45) | |
| 50 mg/kg | oral | ↓ | ||||||
| F | SD rats | NMU | MF | 110-220 mg/kg | diet | ↓ | (46) | |
| Skin | F | SHR mice | BP | MF | 200 mg/L | d.w. | ↓ | (47) |
| F | SHR mice | BP | MF | 200 mg/L | d.w. | ↓ | (48) | |
| F | FVB/N | DMBA + TPA | MF | 2-250 mg/kg | d.w. | ↓ | (49) | |
| Soft tissues | M | Balb/c mice | MCA | PF | 25 mg/kg | oral | ↓ | (50) |
| F | SHR mice | BP | MF | 200 mg/L | d.w. | ↓ | (51) | |
| Uterus | F | F344 rats | Spontaneous | PF | 400-800 ppm | diet | ↓ | (52) |
| F | Balb/c mice | E2, tamoxifen | MF | 50 mg/kg | diet | ↓ | (53) | |
| F | 129/Sv | Spontaneous | MF | 600 mg/L | d.w. | ↓ | (54) | |
| Target organ | Sex | Species, strain | Carcinogenic agent | Drug | Doses | Route | Effect | References |
| Uterine cervix | F | SHR mice | BP | MF | 200 mg/L | d.w. | ↓ | (55) |
| Lung | M&F | A/J mice | NNK | MF | 250 mg/kg | i.p. | ↓ | (56) |
| M&F | LID mice | NNK | MF | 250 mg/kg | d.w. | ↓ | (57) | |
| M | 129/Sv mice | Urethan | MF | 200 mg/L | d.w. | ↓ | (58) | |
| Oral mucosa | F | C57BL/6 mice | 4-NQO | MF | 50 mg/kg | i.p. | ↓ | (59) |
| Pancreas | M | Hamsters | NBOPA | MF | 320 mg/kg | oral | ↓ | (60) |
| M&F | p48Cre/+.LSL-KrasG12D mice | Spontaneous | MF | 1,000-2,000 ppm | diet | ↓ | (61) | |
| Pancreatic islets | M | CD1 mice | HCHFD | MF | 50-250 mg/kg | diet | ↓ | (62) |
| Liver | M | C57BL/6J mice | DENA | MF | 250 mg/kg | diet | ↓ | (63) |
| M | Wistar rats | DENA | MF | 125 mg/kg | oral | ↓ | (64) | |
| M | C57BL/6J mice | Spontaneous | MF | 10 mg/kg | diet | ↓ | (65) | |
| M | C57BL/6 mice | High-fat diet | MF | 250 mg/kg | d.w. | ↓ | (66) | |
| Small intestines | M&F | ApcMin/+ mice | Spontaneous | MF | 250 mg/kg | diet | ↓ | (67) |
| Intestines | M&F | PTEN+/– mice | Spontaneous | MF | 300 mg/kg | d.w. | = | (68) |
| Intestines | M&F | PTEN +/– mice | Spontaneous | PF | 300 mg/kg | d.w. | = | (68) |
| Colon | M&F | BALB/c mice | AOM | MF | 250 mg/kg | diet | ↓ | (69) |
| M | F344 rats | AOM | MF | 15 mg/kg | d.w. | ↓ | (70) | |
| ND | F344 rats | AOM | MF | 500-1,000 ppm | diet | = | (71) | |
| F | LIO rats | DMH | PF | 5 mg/rat | oral | ↓ | (7,16) | |
| Kidney | M&F | LIO rats | NEU, tp | BF | 5 mg/rat | oral | ↓ | (18) |
| Lymphoid tissue | M&F | B6C3F1 | Spontaneous | PF | 300-625 mg/kg | diet | ↓ | (52) |
| M&F | PTEN+/– mice | Spontaneous | MF | 300 mg/kg | d.w. | = | (68) | |
| M&F | PTEN+/– mice | Spontaneous | PF | 300 mg/kg | d.w. | ↓ | (68) | |
| Nervous system | M&F | LIO rats | NMU, t.p. | BF | 5 mg/rat | oral | ↓ | (11) |
| M&F | LIO rats | NEU, t.p. | BF | 5 mg/rat | oral | ↓ | (18) | |
| Total tumors | M&F | F344 rats | Spontaneous | PF | 400-800 ppm | diet | = | (52) |
| M&F | B6C3F1mice | Spontaneous | PF | 400-800 ppm | diet | = | (52) | |
| F | SHR mice | Spontaneous | MF | 600 mg/L | d.w. | = | (44,72) | |
| M&F | 129/Sv mice | Spontaneous | MF | 600 mg/L | d.w. | ↓ | (54) | |
| F | LIO rats | Spontaneous | BF | 5 mg/rat | oral | ↓ | (12) | |
| F | LIO rats | Spontaneous | PF | 2 mg/rat | oral | ↓ | (36) | |
| F | LIO rats | X-rays | PF | 2 mg/rat | oral | ↓ | (17,36) | |
| M | B6C3F1 | Spontaneous | MF | 10 mg/kg | diet | = | (65) | |
| M | C57BL/6 | Spontaneous | MF | 10 mg/kg | diet | = | (65) |
M, males; F, females; ND, no data; d.w., drinking water; i.p., intraperitoneally; t.p., transplacental; AOM, azoxymethane; BP, benzo(a)pyrene; DMBA, 7,12-dimethylbenz(a)anthracene; DENA, N-nitroseodiethylamine; DMH, 1,2-dimethylhydrazine; E2, estradiol-17β; HCHFD, high carbohydrate fat diet; HER-2/neu, transgenic mice; LID, liver IGF-1-deficient; MCA, 20-methylcholanthrene; MMTV, murine mammary tumor virus; NBOPA, N-nitrosobis(2-oxopropyl) amine; NEU, N-nitroso-ethylurea; NMU, N-nitrosomethylurea; NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; 4-NQO, 4-nitoquinoline-1-oxide; TPA, 12-O-tetradeanoyphorbol-13-actate.