|
| Animal model | Carcinogen | CRC-specific endpoints measured |
|
| Studies demonstrating beneficial effects of folate on critical colorectal cancer endpoints |
Rat
Sprague-Dawley
Male
[83] | DMH
44 mg/kg body weight
Weekly × 15 weeks
| Percent of rats with colonic tumors:
70% (0 mg/kg folate)
40% (2 mg/kg folate)
10% (8 mg/kg folate)
42% (40 mg/kg folate)
(Similar results for # tumors/rat) |
|
Rat
Fisher 344
Male
[15] | 5-week diet prior to DMH
ENU
100mg/kg | Mutant frequency:
8-fold increase (0 mg/kg folate, no antibiotics)
6-fold increase (0 mg/kg folate, with antibiotics)
5-fold increase (2 mg/kg folate) |
|
Rat
Fisher 344
Male
[85] | DMH
25 mg/kg body weight
2 weekly injections
| Colonic aberrant crypts/aberrant crypt foci:
~150 aberrant crypts, 50 foci (2 mg/kg folate)
~250 aberrant crypts, 75 foci (0 mg/kg folate) |
|
Rat
Albino
Male
[86] | 3-week diet prior to DMH
8-week diet after DMH
AOM
30 mg/kg body weight | Aberrant crypt foci:
~65 aberrant crypts (2 mg/kg folate)
~58 aberrant crypts (8 mg/kg folate)
~30 aberrant crypts (40 mg/kg folate)
(note: no deficient group) |
|
Mice
Balb/cAnNCrlBR
Wildtype (from 129)
Backcrossed >10 generations into Balb/c
Sex: not stated [81] | None, diet only | Percent mice with duodenal tumors:
0% (2 mg/gk folate)
12.5% (0.3 mg/kg folate)
(2/16 mice; adenoma versus adenocarcinoma not specified) |
|
Mice
C57bl/6
Apc1638N,
BAT-LacZ (Wnt reporter mouse)
No. of generations backcrossed N/A
Sex: not stated
[84] | None, diet and genotype only
(Note: diet includes multiple B vitamin manipulations: Riboflavin, B6, B12, and folate) | Gastrointestinal tumor incidence and multiplicity; aberrant crypt foci:
50% incidence (2 mg/kg folate, adequate Bvitamins)
91% incidence (0 mg/kg folate, B vitamin deficient)
~1.7 tumors/animal (2 mg/kg folate, adequate Bvitamins)
~2.7 tumors/animal (0 mg/kg folate, B vitamin deficient)
~2 aberrant crypts (2 mg/kg folate, adequate Bvitamins)
~2.5 aberrant crypts (0 mg/kg folate, B vitamin deficient) |
|
Mice
C57bl/6
Apc1638N
No. of generations backcrossed N/A
Sex: both
[78] | None, diet and genotype only
(Note: diet includes multiple B vitamin manipulations: Riboflavin, B6, B12, and folate; dietary intervention in dams and offspring) | Gastrointestinal tumor incidence (percent) and multiplicity:
~55% incidence (0.5 mg/kg folate, B vitamin deficient)
~58% incidence (2.0 mg/kg folate, Bvitamin adequate)
~20% incidence (8.0 mg/kg folate, B vitamin supplemented)
~0.6 tumors/animal (0.5 mg/kg folate, B vitamin deficient)
~0.6 tumors/animal (2.0 mg/kg folate, Bvitamin adequate)
~0.25 tumors/animal (8.0 mg/kg folate, B vitamin supplemented)
(Note: tumor invasiveness significantly worse in deficient group compared to control group) |
|
Mice
C57bl/6
Apcmin
>10 generations backcrossed
Sex: not stated
[68] | None, diet and genotype only
Shmt heterozygous and null genotypes crossed onto Apcmin
Note: choline altered as well as folate | Gastrointestinal tumor number and tumor load (total tumor area/mouse):
Impact of diet seen only in Shmt heterozygous model:
~32 small intestinal tumors (2 mg/kg folate, 2.5 g/kg choline)
~60 small intestinal tumors (0 mg/kg folate, 0 g/kg choline)
~40 mm 2 tumor load (2 mg/kg folate, 2.5 g/kg choline)
~80 mm2 tumor load (0 mg/kg folate, 0 g/kg choline) |
|
Mice
C57bl/6
DNA polymerase β +/−
>10 generations
Sex: Male
[59] | DMH
30 mg/kg body weight
Weekly for 6 weeks
Killed after 12 weeks | Total aberrant crypt foci:
~15 aberrant crypts (2 mg/kg folate, wildtype)
~38 aberrant crypts (0 mg/kg folate, wildtype)
(Note: this work presents data both in support of protective and detrimental roles for folate; protective presented here, detrimental presented below) |
|
Rat
Sprague-Dawley
Male
[72] | AOM
15 mg/kg
Weekly for 3 weeks
Killed after 8 weeks | Total aberrant crypt foci:
~300 aberrant crypts (8 mg/kg folate)
~200 aberrant crypts (0 mg/kg folate + abx post-AOM)
(Note: no “standard” control group of 2 mg/kg folate) |
|
Rat
Sprague-Dawley
Male
[73]
| AOM
15 mg/kg/week
Weekly for 3 weeks
Killed after 22 weeks | Number of colon adenocarcinomas:
13 (8 mg/kg folate, no abx)
12 (8 mg/kg folate, with abx)
4 (0 mg/kg folate, no abx)
3 (0 mg/kg folate, abx before AOM)
4 (0 mg/kg folate, abx after AOM)
(Note: no “standard” control group of 2 mg/kg folate) |
|
Rat
Sprague-Dawley
Male
[76] | AOM
2 weekly exposures
(total dosing unclear)
Diet begun 6 weeks post- AOM | Aberrant crypt foci and tumor size (tumor diameter/tumor-bearing animal, cm)
84.6 aberrant crypts (0 mg/kg folate)
93.4 aberrant crypts (2 mg/kg folate)
108.1 aberrant crypts (5 mg/kg folate)
137.9 aberrant crypts (8 mg/kg folate)
0.5 cm (0 mg/kg folate)
1.2 cm (2 mg/kg folate)
1.3 cm (5 mg/kg folate)
1.6 cm (8 mg/kg folate) |
|
Mice
C57bl/6
APCmin
No. of generations backcrossed N/A
Sex: not stated
[77] | None, diet and genotype only
Two timepoints: 3 and 6 months | Aberrant crypt foci and ileal adenomas:
At 3 months:
1.3 aberrant crypts (0 mg/kg folate)
0.27 aberrant crypts (2 mg/kg/folate)
0.20 aberrant crypts (8 mg/kg folate)
0.00 aberrant crypts (20 mg/kg folate)
11.0 ileal adenomas (0 mg/kg folate)
7.36 ileal adenomas (2 mg/kg folate)
7.30 ileal adenomas (8 mg/kg folate)
2.36 ileal adenomas (20 mg/kg folate)
At 6 months:
1.67 ileal adenomas (0 mg/kg folate)
7.09 ileal adenomas (2 mg/kg folate)
5.33 ileal adenomas (8 mg/kg folate)
4.38 ileal adenomas (20 mg/kg folate) |
|
Mice
C57bl/6
DNA polymerase β +/−
>10 generations
Sex: male
[59] | DMH
30 mg/kg body weight
Weekly for 6 weeks
Killed after 12 weeks | Total aberrant crypt foci:
~33 aberrant crypts (2 mg/kg folate, heterozygote)
~20 aberrant crypts (0 mg/kg folate, heterozygote)
(Note: this work presents data both in support of protective and detrimental roles for folate; detrimental presented here, protective presented above.) |
|
