| Species, strain (sex) Age at start Duration Reference | Dosing regimen Animals/group at start No. surviving animals | Results For each target organ: incidence (%) and/or multiplicity of tumours | Significance | Comments |
|---|---|---|---|---|
| Rat, Wistar (M) Age 4 wk 142 wk Alink et al. (1989) | Full carcinogenicity study Rats were fed one of five diets, A–E, ad libitum: diet A, a semi-synthetic rodent diet; diet B, diet A supplemented with fruits and vegetables; diet C, a “humanized” diet consisting of meat (including beef), bread, eggs, and margarine, alone with other semi-synthetic products; diet D, cooked diet C; diet E, diet D, supplemented with fruits and vegetables 50 rats/group 48, 46, 48, 48, 48 | Pituitary gland (pars distalis) | Limitations: tumour data were confounded by the fact that the human diets had approximately twofold more fat and 50% less fibre than the rodent diets; rats fed the human diets weighed considerably more than rats fed the rodent diets An equal number of female Wistar rats were also treated; there were no significant differences in tumour incidence | |
| Tumour incidence: 26/45 (58%), 28/45 (62%), 33/48 (69%)*, 35/46 (76%)*, 35/48 (73%)* | *P = 0.0016 (human diets, diets C, D, and E, vs rodent diets, diets A and B; two-sided Fisher exact test and IARC method) | |||
| Thyroid gland | ||||
| “Light cell” adenoma or carcinoma: Incidence: 3/48 (6%), 1/46 (2%), 3/48 (5%)*, 6/48 (13%)*, 5/46 (11%)* | *P = 0.0014 (human diets, diets C, D, and E, vs rodent diets, diets A and B; two-sided Fisher exact test and IARC method) | |||
| Rat, F344 (F) Age 7 wk 30–34 wk Reddy et al. (1976) | Initiation–promotion study Rats were fed one of four diets: D1, high soybean protein with high corn oil fat; D2, low soybean protein with low corn oil fat; D3, high beef protein with high beef and corn oil fat; D4, low beef protein with low beef fat; half of the rats in each group (28 rats/group) were initiated with DMH: D1 with DMH; D2 with DMH; D3 with DMH; or D4 with DMH 28 rats/group 28, 28, 28, 28, 28, 28, 28, 28 | Ear canal | DMH-initiated rats had a low incidence (≤ 18%) of kidney mesenchymal tumours and adenocarcinoma of the small intestine. DMH (10 mg/kg bw for 20 wk). [Rats treated with DMH had a significantly increased incidence of ear canal and colon tumours compared with control rats, P ≤ 0.02, two-tailed Fisher exact test] The duration of this experiment (30–34 wk) was probably not sufficient to determine if the diets by themselves were tumorigenic | |
| Squamous cell carcinoma: Incidence: 0/28 (0%), 0/28 (0%), 0/28 (0%), 0/28 (0%), 7/28 (25%), 6/28 (21%), 8/28 (29%), 7/28 (25%) | NS | |||
| Colon | ||||
| Tumour incidence: 0/28 (0%), 0/28 (0%), 0/28 (0%), 0/28 (0%), 15/28 (54%), 10/28 (36%), 16/28 (57%), 10/28 (36%) | NS | |||
| Tumour multiplicity (SEM): 0, 0, 0, 0, 0.90 (0.12)*, 0.44 (0.11), 1.00 (0.19), 0.50 (0.14) | *P < 0.05 (significantly different from D2) | |||
| Adenocarcinoma: Multiplicity: 0, 0, 0, 0, 0.58 (0.13), 0.23 (0.10), 0.61 (0.14)*, 0.14 (0.06) | *P < 0.05 (Significantly different from D4) | |||
| Rat, Sprague-Dawley (M) Age, weanling 32 wk Clinton et al. (1979) | Initiation–promotion study Rats were fed one of three diets: 20% soy protein with 20% beef tallow, 20% raw beef protein with 20% beef tallow, or 20% charcoal-broiled beef protein with 20% beef tallow, fed ad libitum After 4 wk, all the rats were initiated with DMH (1.25 mg/kg bw for 18 wk) 30 rats/group 29, 30, 28 | Small intestine | Limitations: histopathological examination not conducted | |
| Tumour incidence: 9/28 (32%), 12/30 (40%), 8/29 (28%) | ||||
| Tumour multiplicity: 1.1, 1.3, 1.1 | P = 0.17 (number of tumours per tumour-bearing rat, Pearson χ2) | |||
| Colon | ||||
| Tumour incidence: 11/28 (39%), 13/30 (43%), 12/29 (41%) | P = 0.96 (distribution of colon tumour frequency, Neyman χ2) | |||
| Tumour multiplicity: 1.3, 1.4, 1.4 | Tumour multiplicity was reported as No. of tumours per tumour-bearing rat | |||
| Rat, Wistar (M) Age 4 wk 8 mo Alink et al. (1993) | Initiation–promotion study Rats were fed one of five diets, A–E: diet A, a semisynthetic rodent diet; diet B, diet A supplemented with fruits and vegetables; diet C, a “humanized” diet consisting of meat (beef, pork, and chicken), bread, eggs, and margarine, along with other semisynthetic products; diet D, diet C, that had been cooked; or diet E, diet D, supplemented with fruits and vegetables; fed ad libitum 45 rats/group | Colon | All rats were initiated with DMH (10 weekly injections of 50 mg/kg bw) | |
| Adenoma, incidence: 27/43 (63%), 14/36 (39%), 20/42 (48%), 20/43 (47%), 23/43 (53%) | ||||
| Total adenomas: 68, 19, 31, 45, 42 | ||||
| Adenocarcinoma, incidence: 31/43 (72%), 22/36 (61%), 28/42 (67%)*, 34/43 (79%)*, 35/43 (81%)* | Combined groups C,D, and E significantly higher (*P < 0.05; Fisher's exact test) than combined groups A and B Zymbal's gland tumours were also observed, with the incidence being significantly (P < 0.05; Fisher's exact test) greater in the combined C, D, and E diet groups compared to the combined A and B groups; specific incidences, NR | |||
| Total adenocarcinomas: 67, 42, 70, 72, 100 | ||||
| Rat, presumably Sprague-Dawley (NR) Age NR NR McIntosh (1993) | Initiation–promotion study Diet containing red meat protein, whey protein, casein protein, soy protein, or fish protein; fed ad libitum 10 rats/group 10, 10, 10, 10, 10 | Intestine | Limitations: histopathological examination not conducted Rats were fed one of five diets: 20% protein derived from red meat [type not specified], 20% protein derived from whey, 20% protein derived from casein, 20% protein derived from soy, or 20% protein derived from fish All the rats were initiated with DMH (3 weekly injections of 20 mg/kg bw) | |
| Tumour incidence: 60%, 20%, 40%, 50%, 40% | Incidence of intestinal tumours, NS (may be a consequence of the small number of animals per group) | |||
| Tumour multiplicity: 1.1, 0.2*, 0.4, 0.9, 0.8 | Decrease; *P < 0.05 (No. of intestinal tumours per rat; whey protein diet vs red meat protein, soy protein, or fish protein diet; statistical test not specified) | |||
| Rat, Sprague-Dawley (M) Age 5 wk 6 mo McIntosh et al. (1995) | Initiation–promotion study Diet containing casein (20.0 g/100 g diet), whey protein concentrate (21.3 g/100 g diet), kangaroo skeletal muscle (22.8 g/100 g diet), or defatted soybean meal (33.3 g/100 g diet), fed ad libitum 20 rats/group Survival: NR | Large intestine | Limitations: histopathological examination not conducted All rats were initiated with DMH (3 weekly injections of 15 mg/kg bw) | |
| Total tumours: 6*, 5*, 10, 21 | Decrease; *P < 0.02 (tumours per group, casein and whey protein diets vs kangaroo meat and defatted soybean meal diets, regression analysis using Poisson distribution) | |||
| Intestine | ||||
| Tumour incidence: 45%, 30%, 50%, 60% | P = 0.15 (No. of surviving rats, NR, all presumed to have survived; χ2) | |||
| Total tumours: 12*, 7*, 21, 26 | Decrease; *P < 0.005 (tumours per group, casein and whey protein diets vs kangaroo meat and defatted soybean meal diets, regression analysis using Poisson distribution) | |||
| Rat, Sprague-Dawley (M) Age, weanling 27 wk Pence et al. (1995) | Initiation–promotion study Diet containing casein protein with 5% corn oil, casein protein with 20% corn oil, casein protein with 5% beef tallow, casein protein with 20% beef tallow, beef protein with 5% corn oil, beef protein with 20% corn oil, beef protein with 5% beef tallow, or beef protein with 20% beef tallow; fed ad libitum 25 rats/groups Survival: NR | Small intestine | Rats were fed AIN-76A–based test diets using a 2 × 2 × 2 factorial design, with the factors being the protein source (casein or lean beef), fat source (corn oil or beef tallow), and fat level (5% or 20%) Rats were initiated with DMH (10 weekly injections of 20 mg/kg bw) Ten rats per diet group served as vehicle controls; tumour incidence in the controls was NR The duration of this experiment (27 wk) was probably not sufficient to determine if the diets by themselves were tumorigenic | |
| Adenoma incidence: 4%, 0%, 4%, 0%, 0%, 0%, 0%, 7% | ||||
| Adenocarcinoma, incidence: 48%, 28%, 40%, 24%, 32%, 28%, 48%, NR | ||||
| Adenoma or adenocarcinoma, incidence: 32%, 48%, 28%, 40%, 24%, 32%, 28%, 52% | ||||
| Colon | ||||
| Adenoma, incidence: 24%, 20%, 24%, 36%, 16%, 40%, 12%, 29% | ||||
| Adenocarcinoma, incidence: 60%*, 48%*, 32%*, 40%*, 20%, 16%, 28%, 19% | *P < 0.05 (casein protein diets vs beef, except 5% beef tallow, diets, irrespective of fat source; χ2) | |||
| Adenoma or adenocarcinoma, incidence: 64%, 52%, 52%, 64%, 28%*, 52%, 36%, 42% | Decrease; *P < 0.05 (beef protein with 5% corn oil diet vs 5% casein protein with 5% corn oil diet, χ2) | |||
| Colon and small intestine | ||||
| Adenoma or adenocarcinoma, incidence: 72%, 72%, 56%, 80%, 48%, 64%, 44%, 67% | ||||
| Rat, Sprague-Dawley (M) Age, weanling 27 wk Lai et al. (1997) | Initiation–promotion study Rats were fed an AIN-76A–based diet containing casein (protein source) with corn oil or lean ground beef (protein source) with corn oil, fed ad libitum 30 rats/group 28, 28 | Small intestine | Rats were initiated with DMH (10 weekly injections of 20 mg/kg bw) Five rats per diet group served as vehicle controls; tumour incidence in the controls was NR The duration of this experiment (27 wk) was probably not sufficient to determine if the diets by themselves were tumorigenic | |
| Adenocarcinoma: Incidence: 15/28 (52%), 18/28 (62%) | NS (χ2) | |||
| Multiplicity: 0.66, 0.90 | NS (No. of tumours per rat, Student t test) | |||
| Colon
Adenocarcinoma: | ||||
| Incidence: 18/28 (62%), 15/28 (52%) | NS (appears that two rats from each group were removed early and not included in the final tumour assessment, χ2) | |||
| Multiplicity: 0.86, 0.79 | NS (No. of tumours per rat, Student t test) | |||
| Colon or small intestine | ||||
| Adenocarcinoma: Incidence: 23/28 (79%), 24/28 (83%) | NS (χ2) | |||
| Multiplicity: 1.52, 1.69 | NS (No. of tumours per rat, Student t test) | |||
| Rat, Sprague-Dawley (M) Age, weanling 27 wk Pence et al. (1998) | Initiation–promotion study Diet containing low fat with low HAAs, then low fat; high fat with high HAAs, then high fat with high HAAs; low fat with low HAAs, then low fat with high HAAs; high fat with low HAAs, then high fat; low fat with high HAAs, then low fat with high HAAs; low fat with high HAAs, then low fat; high fat with high HAAs, then low fat; or high fat with high HAAs, then high fat; fed ad libitum 25 rats/group Survival, NR | Stomach | Rats were fed one of four AIN-76A–based diets: low-fat (5%) with low-HAA (6.6 ng) beef, high-fat (20%) with low-HAA beef, low-fat with high-HAA (85.6 ng) beef, or high-fat with high-HAA beef Rats were initiated with DMH (10 weekly injections of 20 mg/kg bw). Ten rats on the high-fat, high-HAA diet did not receive DMH; these rats did not develop tumours The duration of this experiment (27 wk) was probably not sufficient to determine if the high-fat, high-HAA diet by itself was tumorigenic | |
| Tumour incidence: 4%, 8%, 0%, 4%, 16%, 8%, 8%, 12% | NS | |||
| Tumour multiplicity: 0.04, 0.08, 0.00, 0.04, 0.16, 0.08, 0.08, 0.12 | ||||
| Small intestine | ||||
| Tumour incidence: 20%, 28%, 48%, 46%, 32%, 24%, 16%, 36% | NS | |||
| Tumour multiplicity: 0.36, 0.28, 0.56, 0.58, 0.56, 0.24, 0.24, 0.40 | ||||
| Colon | ||||
| Adenoma or adenocarcinoma: Incidence: 76%, 56%*, 60%, 83%, 88%, 84%, 56%*, 56%* | Decrease; *P < 0.05 (high-fat with high-HAA diets, incidence, 56%, vs low-fat with high-HAA diets, incidence, 84–88%] during wk 1–12, χ2) | |||
| Multiplicity: 1.20, 0.68, 0.96, 1.13, 1.40, 1.04, 0.76, 0.68 | ||||
| Rat, F344 (F) Age 5 wk 15 wk Parnaud et al. (1998) | Initiation–promotion study Diet containing low casein with lard, low casein with olive oil, low beef, low chicken, low bacon, high casein with lard, high casein with olive oil, high beef, high chicken, or high bacon; fed ad libitum 10 rats/group 10, 10, 10, 10, 10, 10, 10, 9, 10, 10 | Colon | Rats were fed low-meat or high-meat diets; fat and protein were provided by beef, chicken, bacon, olive oil, or lard; there were two control diets, where fat was provided by lard or olive oil, and protein provided by casein The rats received a single injection of azoxymethane (20 mg/kg bw) | |
| No. of crypts per ACF, mean (SD): 3.21 (0.47), 3.11 (0.28), 3.25 (0.44), 3.16 (0.34), 2.84 (0.45), 3.27 (0.38), 2.94 (0.30), 3.15 (0.59), 3.18 (0.32), 2.62 (0.60)* | The high bacon diet was lower than high casein & lard diet (*P < 0.001; ANOVA and Dunnett's test) | |||
| No. of ACF per rat, mean (SD): 65 (34), 83 (30), 69 (23), 76 (37), 86 (47), 75 (44), 61 (43), 71 (25), 98 (30), 72 (37) | ||||
| Rat, F344 (F) Age 5 wk 45 days Parnaud et al. (2000) | Initiation–promotion study AIN-76 diet containing 28% fat (corn oil) and 40% protein (casein) with azoxymethane (20 mg/kg bw); AIN-76 diet containing 28% fat (corn oil) and 40% protein (casein); AIN-76 diets with 60% bacon 5, 10, 10 rats/group 5, 10, 10 | Colon | The duration of this experiment (45 days) was probably not sufficient to determine if the diets by themselves were tumorigenic | |
| No. of ACF per colon, mean (range): 9 (7–154), 0, 0 | ||||
| Rat, F344 (F) Age 5 wk 100 days Parnaud et al. (2000) | Initiation–promotion study Rats were fed one of five AIN-76–based diets containing casein, beef, chicken, pork, or bacon; fed ad libitum 10 rats/group 10, 10, 10, 10, 10 | Colon | All rats were treated with a single injection of azoxymethane (20 mg/kg bw) | |
| No. of aberrant crypts per ACF, mean (SD): 2.9 (0.2), 2.9 (0.3), 2.7 (0.2), 2.7 (0.3), 2.4 (0.2)* | Decrease; *P < 0.01 (No. of aberrant crypts per ACF, bacon diet vs casein diet, ANOVA and Dunnett test) | |||
| No. of ACF per colon, mean (SD): 137 (26), 122 (60), 151 (28), 151 (25), 134 (21) | ||||
| No. of ACF with > 7 crypts per ACF, mean (SD): 19.7 (6.8), 15.6 (9.8), 18.6 (8.1), 18.1 (6.8), 11.1 (4.4)* | Decrease; *P = 0.003 (No. of ACF with > 7 crypts per ACF, bacon diet vs casein diet, ANOVA and Dunnett test) | |||
| Rat, Wistar (NR) Age 13 wk 14 wk Belobrajdic et al. (2003) | Initiation–promotion study Rats were fed one of six AIN-93–modified diets consisting of 8%, 16%, or 32% red meat, 8%, 16%, or 32% whey; fed ad libitum 12 rats/group Survival: NR | Proximal colon | Red meat was barbecued kangaroo muscle meat Each group presumably consisted of 12 rats, although this was not stated explicitly All rats were treated with two weekly injections of azoxymethane (15 mg/kg bw) | |
| No. of ACF per rat, mean: 90, 71, 84, 61, 77, 52 | Numbers of ACF estimated from histogram | |||
| No. of single ACF per rat, mean: 32, 33*, 34*, 25, 26, 16 | *P < 0.05 (No. of single ACF per rat, numbers estimated from histogram; 16% and 32% red meat diets vs 32% whey protein diet; ANOVA and Tukey multiple comparison test) | |||
| Rat, Sprague-Dawley (M) NR (weight, 50–75 g) 11 wk Khil & Gallaher (2004) | Initiation–promotion study Rats were fed one of four AIN-93G–modified diets using a 2 × 2 factorial design,: casein with soybean oil, beef with soybean oil, casein with tallow, or beef with tallow; fed ad libitum 14 rats/group 14, 14, 14, 14 | Colon | Casein and beef were the protein sources, and soybean oil and tallow were the fat sources; the diets were balanced for protein and fat energy content All rats were treated with two injections of DMH (15 mg/kg bw) | |
| No. of ACF per cm2, mean (SEM): 2,98 (0.50), 3.45 (0.37), 1.89 (0.39)*, 2.87 (0.44)* | Decrease; *P = 0.043 (No. of ACF per cm2, tallow diets vs soybean oil diets, ANOVA and Duncan multiple range test) | |||
| No. of aberrant crypts per ACF, mean (SEM): 3.08 (0.19), 2.69 (0.11), 3.56 (0.35), 2.81 (0.08) | ||||
| No. of aberrant crypts per cm2, mean (SEM): 9.61 (1.98), 9.46 (1.18), 7.02 (1.54), 8.26 (1.45) | ||||
| Rat, F344 (F) Age 5 wk 15 wk Pierre et al. (2004) | Initiation–promotion study ControlAIN-76 diet or modified diet containing skinless chicken meat (600 g/kg diet), beef meat (600 g/kg diet), black pudding (blood sausage, 600 g/kg diet), or powdered bovine haemoglobin (6.3 g/kg diet); fed ad libitum 20, 10, 10, 10, 10 rats/group 20, 10, 10, 10, 10 | Colon | All rats were treated with azoxymethane (20 mg/kg bw) All the diets were balanced for protein, fat, calcium, and iron | |
| No. of crypts per ACF, mean (SD): 2.7 (0.4), 2.9 (0.4)*, 2.8 (0.2), 3.1 (0.5)*, 2.9 (0.2)* | *P < 0.05 (No. of crypts per ACF; chicken, haemoglobin, and black pudding diets vs control diet; ANOVA and Fisher LSD test) | |||
| Total ACF crypts per colon, mean (SD): 192 (55), 267 (65)*, 280 (49)*, 285 (78)*, 301 (48)* | *P < 0.05 (No. of ACF crypts per colon; chicken, beef, haemoglobin, and black pudding diets vs control diet; ANOVA and Fisher LSD test) | |||
| No. of ACF per colon, mean (SD): 72 (16), 91 (18)*, 100 (13)*, 93 (24)*, 103 (14)* | *P < 0.05 (No. of ACF per colon; chicken, beef, haemoglobin, and black pudding diets vs control diet; ANOVA and Fisher LSD test) | |||
| No. of crypts per MDF, mean (SD): 4.65 (2.40), 4.92 (1.64), 4.23 (1.15), 4.60 (1.93), 4.29 (0.59) | ||||
| Total MDF crypts per colon, mean (SD): 2.9 (4.0), 6.0 (3.9), 8.5 (6.9)*, 11.5 (9.0)*, 13.1 (6.0)*,** | *P < 0.05 (No. of MDF crypts per colon; beef, haemoglobin, and black pudding diets vs control diet; ANOVA and Fisher LSD test) **P < 0.05 (black pudding diet vs beef and chicken diets, ANOVA and Fisher LSD test) | |||
| No. of MDF per colon, mean (SD): 0.55 (0.68), 1.20 (0.63), 1.90 (1.37)*, 2.40 (1.50)*, 3.00 (1.24)*,** | *P < 0.05 (No. of MDF per colon; beef, haemoglobin, and black pudding diets vs control diet; ANOVA and Fisher LSD test) **P < 0.05 (black pudding diet vs beef and chicken diets, ANOVA and Fisher LSD test) | |||
| Rat, F344 (F) Age 5 wk 15 wk Pierre et al. (2008) | Initiation–promotion study The rats were fed one of eight AIN-76–modified diets: a low-calcium control diet; a low-calcium, beef meat diet; a high-calcium control diet; a high-calcium, beef meat diet; an olive oil–fortified control diet; an olive oil–fortified, beef meat diet; an antioxidant-fortified control diet; or an antioxidant-fortified, beef meat diet; fed ad libitum 10 rats/group 10, 10, 10, 10, 10, 10, 10, 10 | Colon | All rats were treated with a single injection of DMH (190 mg/kg bw) All the diets were balanced for protein, fat, and iron | |
| No. of crypts per ACF, mean (SD): 2.3 (0.2), 2.6 (0.2)*, 2.8 (0.2)**, 2.5 (0.2), 2.5 (0.2), 2.4 (0.2), 2.3 (0.2), 2.4 (0.3) | *P < 0.05 (No. of crypts per ACF, beef with low-calcium diet vs respective control diet, ANOVA and Fisher LSD test) **P < 0.05 (control diet with high calcium vs other control diets, ANOVA and Fisher LSD test) | |||
| No. of ACF per colon, mean (SD): 105 (24), 137 (26)*, 130 (22)**, 106 (24), 104 (25), 125 (20)*, 107 (22), 127 (22)* | *P < 0.05 (No. of ACF per colon; beef, except beef with high calcium, diets vs respective control diets; ANOVA and Fisher LSD test) **P < 0.05 (control diet with high calcium vs other control diets, ANOVA and Fisher LSD test) | |||
| No. of ACF crypts per colon, mean (SD): 245 (52), 347 (55)*, 365 (71)**, 265 (74), 258 (71), 299 (60)*, 243 (48), 300 (40)* | *P < 0.05 (No. of ACF crypts per colon; beef, except beef with high calcium, diets vs respective control diets; ANOVA and Fisher LSD test) **P < 0.05 (control diet with high calcium vs other control diets, ANOVA and Fisher LSD test) | |||
| No. of crypts per MDF, mean (SD): 4.6 (1.7), 5.3 (1.6), 7.6 (2.4)*, 7.8 (3.1), 4.0 (1.2), 4.3 (0.7), 4.4 (1.4), 3.9 (1.4) | *P < 0.05 (No. of crypts per MDF, control diet with high calcium vs other control diets, ANOVA and Fisher LSD test) | |||
| No. of mucin-depleted crypts per colon, mean (SD): 18.2 (15.3), 40.7 (18.9)*, 58.1 (27.5)**, 24.3 (12.6), 15.6 (13.0), 22.5 (5.3), 14.7 (8.8), 22.4 (9.5) | *P < 0.05 (No. of mucin-depleted crypts per colon, beef with low-calcium diet vs respective control diet, ANOVA and Fisher LSD test) **P < 0.05 (control diet with high calcium vs other control diets, ANOVA and Fisher LSD test) | |||
| No. of MDF per colon, mean: 3.5 (2.0), 7.4 (2.0)*, 7.6 (3.0)**, 3.4 (1.8), 3.8 (2.5), 5.3 (1.2)*, 3.2 (1.3), 5.6 (1.1)* | *P < 0.05 (No. of MDF per colon; beef, except beef with high calcium, diets vs respective control diets; ANOVA and Fisher LSD test) **P < 0.05 (control diet with high calcium vs other control diets, ANOVA and Fisher LSD test) | |||
| Rat, F344 (F) Age 5 wk 15 wk Pierre et al. (2010) | Initiation–promotion study AIN-76–modified control diet or diet containing ham (550 g/kg diet), balanced for protein, fat, and iron; fed ad libitum 10 rats/group 10, 10 | Colon | All rats were treated with a single injection of DMH (190 mg/kg bw) | |
| No. of crypts per ACF, mean (SD): 2.3 (0.2), 2.1 (0.1) | ||||
| No. of ACF per colon, mean (SD): 105 (24), 119 (16)* | *P < 0.05 (No. of ACF per colon, ham diet vs control diet, ANOVA and Tukey multiple comparison test) | |||
| No. of crypts per MDF, mean (SD): 4.6 (1.7), 4.3 (1.2) | ||||
| No. of MDF per colon, mean (SD): 3.5 (2.0), 8.5 (2.2)* | *P < 0.05 (No. of MDF per colon, ham diet vs control diet, ANOVA and Tukey multiple comparison test) | |||
| Rat, F344 (F) Age 5 wk 15 wk Santarelli et al. (2010) | Initiation–promotion study The rats were fed a control diet or one of four AIN-76–modified diets: dark cooked meat with nitrite, oxidized; dark cooked meat with nitrite, anaerobic; dark cooked meat, oxidized; or dark raw meat, anaerobic; fed ad libitum 10 rats/group 10, 10, 10, 10, 10 | Colon | All rats were treated with a single injection of DMH (180 mg/kg bw) The dark meat was pork meat with high haem The diets were balanced for protein and fat | |
| No. of ACF per colon, mean (SD): 81 (18), 100 (16)*, 102 (25)*, 106 (21)*, 101 (17)* | *P < 0.05 (No. of ACF per colon, experimental dark meat diets vs control diet, ANOVA and Fisher LSD test) | |||
| No. of crypts per MDF, mean (SD): 3.9 (1.5), 4.2 (1.2), 2.7 (1.7)*, 3.5 (1.2), 3.9 (1.9) | Decrease; *P < 0.05 (No. of crypts per MDF; dark cooked meat with nitrite, anaerobic diet vs control and dark cooked meat, oxidized diets; ANOVA and Fisher LSD test) | |||
| No. of MDF per colon, mean (SD): 2.9 (1.9), 4.1 (2.9)*, 2.1 (2.0), 2.8 (2.8), 3.4 (2.6) | *P < 0.05 (No. of MDF per colon; dark cooked meat with nitrite, oxidized diet vs control diet; Fisher LSD test) | |||
| No. of mucin-depleted crypts per colon, mean (SD): 11 (8), 18 (13)*, 8 (8), 10 (11), 14 (10) | *P < 0.05 (No. of mucin-depleted crypts per colon; dark cooked meat with nitrite, oxidized diet vs control; dark cooked meat with nitrite, anaerobic; and dark cooked meat, oxidized diets; ANOVA and Fisher LSD test) | |||
| Rat, F344 (F) 5 wk 15 wk Pierre et al. (2013) | Initiation–promotion study One of three AIN-76–modified diets containing dark cooked meat with nitrite, oxidized by air; dark cooked meat with nitrite, oxidized by air and fortified with α-tocopherol; or dark cooked meat with nitrite, oxidized by air and fortified with CaCO3; fed ad libitum 16, 10, 10 rats/group 16, 10, 10 | Colon | All rats were treated with a single injection of DMH (180 mg/kg bw) The dark meat was pork meat with high haem | |
| No. of ACF per colon, mean (SD): 126 (20), 125 (15), 124 (24) | ||||
| No. of crypts per MDF, mean (SD): 3.7 (1.3), 2.4 (2.1), 2.5 (1.4) | ||||
| No. of MDF per colon, mean (SD): 2.7 (2.1)*, 1.4 (1.5), 1.3 (1.6) | *P < 0.05 (No. of MDF per colon; dark cooked meat treated with nitrite, oxidized by air diet vs dark cooked meat treated with nitrite, oxidized by air and fortified with α‑tocopherol or dark cooked meat treated with nitrite, oxidized by air and fortified with CaCO3 diet; Fisher LSD test) | |||
| Rat, F344 (F) Age 5 wk 15 wk Santarelli et al. (2013) | Initiation–promotion study Low-calcium AIN-76–modified diets, either 40% hot dog [pork] meat or 50% French saucisson [pork]; the diets were balanced for protein, fat, and iron; fed ad libitum 10 rats/group 10, 10, 10 | Colon | All rats were treated with a single injection of DMH (180 mg/kg bw) | |
| No. of ACF per colon, mean (SD): 110 (17), 108 (32), 102 (25) | ||||
| No. of crypts per MDF, mean (SD): 2.6 (2.4), 4.7 (2.4)*, 3.2 (2.2) | *P < 0.05 (No. of crypts per MDF, hot dog with low-calcium diet vs control diet, ANOVA and Fisher LSD test) | |||
| No. of MDF per colon, mean (SD): 1.2 (1.4), 3.0 (1.7)*, 2.4 (2.4) | *P < 0.05 (No. of MDF per colon, hot dog with low-calcium diet vs control diet, ANOVA and Fisher LSD test) | |||
| Rat, F344 (F) Age 5 wk 15 wk Santarelli et al. (2013) | Initiation–promotion study AIN-76–modified diet containing 40% hot dog [pork] with either low or high calcium (balanced for protein, fat, and iron), fed ad libitum 10 rats/group 10, 10 | Colon | All rats were treated with a single injection of DMH (180 mg/kg bw) | |
| No. of crypts per MDF, mean (SD): 3.5 (0.6), 3.3 (0.4) | ||||
| No. of MDF per colon, mean (SD): 2.3 (1.4)*, 1.2 (1.1) | *P < 0.05 (No. of MDF per colon, hot dog with low-calcium diet vs hot dog with high-calcium diet, ANOVA and Fisher LSD test) | |||
| No. of ACF per colon, mean (SD): 136 (25), 118 (19) | ||||
* or **, statistically significant; ACF, aberrant crypt foci; AIN, American Institute of Nutrition; ANOVA, analysis of variance; CaCO3, calcium carbonate; DMH, dimethylhydrazine; F, female; HAA, heterocyclic aromatic amine; LSD, least significant difference; M, male; MDF, mucin-depleted foci; mo, month; NR, not reported; NS, not significant; SD, standard deviation; SEM, standard error of the mean; vs, versus; wk, week
From: 3. CANCER IN EXPERIMENTAL ANIMALS
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