Table 1.
Tumor Incidence Studies
| METHODS | RESULTS | ||||||
|---|---|---|---|---|---|---|---|
| Study | Reference | Rodent Model |
Tumor Type / Induction model |
Exercise Protocol | Tumor Incidence Results | ||
| Exercise Modality | Exercise Prescription Freq/week | Dur | Intens | Length |
Exercise Initiation | |||||
| Andrianopoulos, 1987 |
25 | 5w old male Sprague- Dawley rats |
Intestinal / DMH, i.p. q1w for 6w |
Voluntary wheel running |
Wheel running | 1w prior to first injection | -Tumors present in 18/20 SED rats and 6/11 EX rats |
| Reddy, 1988 | 33 | Male F344 rats |
Intestinal / Subcutaneous AOM 15mg/kg BW, q1wx2w at 7 wk of age. |
Voluntary wheel running |
Wheel running for 38 weeks | 4d post-AOM | -EX ↓ incidence and multiplicity adenocarcinomas, and liver foci. of colon and |
| Sugie, 1992 | 35 | 5w old F-344 rats |
Hepatocellular / 15 mg/kg AOM s.c. q1w for 2w |
Voluntary wheel running |
38w | 4d post-injection. | -Liver tumors noted in 7% of AOM treated SED only. |
| Ikuyama, 1993 | 28 | Jc1:Wistar rats |
Hepatoma / 0.0177 g/day/kg BW dietary 3'- Me-DAB for 35 weeks. |
Voluntary wheel running |
Wheel running for 62 weeks, using food as a reward for achieving specified distances |
17w prior to dietary 3'-Me- DAB |
-65% reduction in tumor incidence. |
| Zhu, 2008 | 42 | 21d old female Sprague- Dawley rats |
Mammary / 25 or 50 mg/kg MNU, i.p. |
Voluntary wheel running |
Voluntary wheel running for 8w | 1w post-injection | -84.5% incidence vs 98.1%, (SED vs. EX) |
| Esser, 2009 | 27 | C3(1)Tag mice |
Prostate / Transgenic mouse model |
Voluntary wheel running |
Wheel running for 10 weeks Data analyzed based on mice that ran >5K or <5K a day |
10w of age | -18% (>5K) and 55% (<5K) of animals with high grade neoplasia at 20 weeks -57% reduction in incidence of high grade neoplasia in >5K vs <5K mice |
| Alessio, 2009 | 24 | 3w old female Sprague- Dawley rats |
Spontaneous tumors | Voluntary wheel running or activity box |
Wheel: every other day, 24h access throughout animals’ life Activity box (PA): 1h in large activity box twice a week for life. |
Spontaneous tumors, animals followed for life. |
-During weeks 60–120, 38% of EX rats were tumor-bearing animals (vs. 42% PA rats and 54% SED rata). -At week 88, tumor multiplicity was 0.69 for EX animals, 0.75 for PA, and 0.96 for SED. |
| Colbert, 2009 | 26 | Female heterozygous (p53+/−): MMTV-Wnt- 1 transgenic mice |
Mammary / Transgenic | Voluntary wheel running and forced treadmill running |
Treadmill running: TREX 1: 5×|45min|20m/min at 5% grade|until completion TREX 2: 5×|45min|24m/min at 5% grade|until completion Voluntary wheel running with 24 hour access. |
11w of age | -Tumor incidence ↑ in wheel running mice by 32% |
| Mann, 2010 | 31 | 21d old female Sprague- Dawley rats |
Mammary / 50 mg/kg MNU i.p. |
Voluntary non- motorized and motorized wheel running |
Voluntary non-motorized and motorized (40m/min) wheel running |
1w post-injection | -96%, 74% and 70% incidence in controls, non-motorized and motorized mice, respectively |
| Zhu, 2012 | 43 | 21d old female Sprague- Dawley rats |
Mammary / 50 mg/kg MNU i.p. |
Voluntary wheel running at a fixed daily distance |
Three levels: WR-High: maximum 3500m/d WR-Low: maximum 1750m/d. SED control. |
1w post-injection | -97% tumor incidence in controls, 80% tumor incidence in WR-High -Cannot compare WR-High and WR-Low, because dietary energy restriction was applied to WR-Low only |
| Thorling, 1993 | 36 | 5w old male Fischer rats |
Intestinal / 15mg/kg AOM s.c. on Days 1, 4 and 8. |
Forced treadmill running |
5×|2km/day|7m/min|38w. First week was acclimatization. |
3d after last injection | -EX ↓ colon neoplasia incidence, 53% vs 78% in |
| Woods, 1994 | 40 | 6w old male C3H/HeN mice |
Mammary / 2.5 ×105 mammary SCA-1 cells s.c. in the back. |
Forced treadmill running |
Treadmill running: Moderate: 7×|30min|18m/min at 5% grade|1w. Exhaustive: 7×|varied|18m/min for 30min, then 3m/min↑ every 30min until exhausted|1w |
3d prior to injection. | -Increase in tumor incidence at Day 7 in both EX groups, but no differences in any subsequent time points. |
| Whittal, 1996 | 38 | 21d old female Sprague- Dawley Rats |
Mammary / 50 mg/kg NMU i.p. at 50d of age |
Forced treadmill running |
Progressive training to 5×|60min|18 m/min at 15% grade|4w |
21d of age (29d prior to injection) |
-Incidence/multiplicity at 24w post-NMU: 58 tumors in SED rats, 33 tumors in EX rats -No significant difference in latency or incidence |
| Whittal-Strange, 1998 |
39 | 21d old female Sprague- Dawley rats |
Mammary / 37.5mg/kg NMU i.p. at 50d of age, (1 day after last bout of EX) |
Forced treadmill running |
Progressive training to 5×|60min|18 m/min at 15% grade|4w |
21d of age (29d prior to injection) |
-Incidences of carcinomas, high grade and low grade tumors were 29.2%, 10.4%, and 25% in SED, and 38%, 14.3% and 21.4% in EX |
| Westerlind, 2003 |
37 | 21d old female Sprague- Dawley rats |
Mammary / 25 or 50 mg/kg MNU, i.p. |
Forced treadmill running |
Week 1: 5×|10–15min|30m/min|1w. Week 2–9: 5×|30min|23– 25m/min|8w |
1w post-injection | -↑ Latency in EX (35.8d vs. 33.1d). -No difference in median tumor-free survival time was observed in the EX versus sham-EX (SHAM), nor were there any differences in multiplicity at either a high or moderate dose of MNU |
| Zielinski, 2004 | 44 | 6–8w old female BALB/c mice |
Neoplastic Lymphoid cells / 2×107 EL-4 cells s.c. in the back behind the neck |
Forced treadmill running |
7×|3h or until volitional fatigue|gradually increasing speed, 20–40m/min, 5% grade|5–14d |
First session immediately before injection. |
-EX ↓ tumor appearance |
| Zhu, 2009 | 41 | 21d old female Sprague- Dawley rats |
Mammary / 50 mg/kg MNU, i.p. |
Forced wheel running | Motorized running wheel; details not provided |
1w post-injection | -66.7% and 92.6% incidence in EX and SED |
| Kato, 2011 | 29 | 5w old male Fischer 344 rats |
Renal / 5mg/kg BW Fe- NTA i.p. once a day for 7 days, then 10mg/kg Fe-NTA 3×/wk for 11w. |
Forced treadmill running |
Short-term: 15m|8m/min, 0%|12w. Long-term: 15m|8m/min, 0%|12w; then 5×|30m|8m/min, 0%|12w for a total of 24w training Exercise continued until 40 weeks, but at lower intensity to account for the decline in rat health. |
Training done 15m before each injection |
-No differences in number of rats with nodules, nodules/rat or mean area of nodules. -Short-term EX ↑ rats with microcarcinomas, - Long-term EX ↓ rats cinomas, karyomegalic cells and degenerative tubules compared to with microcar short-term. |
| Malicka, 2015 | 45 | 4w old female Sprague Dawley rats |
Mammary / 180 mg/kg MNU i.p. |
Forced treadmill running |
Low intensity (LIT): 5×|10– 35min|0.48–1.34 km/h|12w Moderate intensity (MIT): 5×|10– 35min|0.6–1.68 km/h|12w High intensity (HIT): 5×|10– 35min|0.72–2.0 km/h|12w |
Immediately after MNU injection |
-Incidence 64%, 67%, 40% and 43% in SED, LIT, MIT and HIT groups, respectively (Not significant) -Multiplicity: Rats with tumors had an average of 2.4, 1.6, 1 and 1 tumors in SED, LIT, MIT and HIT groups, respectively (Statistics not performed.) |
| Piguet, 2015 | 46 | 7–9w old male AlbCrePten flox/flox mice |
Hepatocellular carcinoma / Transgenic |
Forced treadmill running |
5w acclimation period followed by: 5×|60m|12.5m/min|27w |
7–9w of age | -Tumor incidence 100% in SED vs. 71% in EX |
| Lunz, 2008 | 30 | 11w old male Wistar Rats |
Intestinal / 4 s.c. injections DMH 3 days apart. |
Forced swimming with 0%, 2% or 4% BW load |
Week 1–2: 5×|5–20min|- load|2w Week 3–5: 5×|5–20min|+ load|3w Week 6– 35: 5×|20min|+load|30w |
24h post first injection | -No difference in tumor incidence -Aerobic swimming training with 2% body weight of load protected against the DMH-induced preneoplastic colon lesions, but not against tumor development in the rat |
| Paceli, 2012 | 32 | Adult male Balb/c mice |
Lung / 1.5mg/kg BW urethane i.p. twice, 2 days apart |
Forced swimming | Aerobic: 4×|20m|--|19w Week 1: 10m/d to 50m in 5 days Anaerobic: 3×|20m (2m swimming/2m resting)|progressive loading of 5– 20%BW|20w |
Within a week after injection | -No significant effects of aerobic training on lung cancer incidence. -Aerobic training resulted in 8 lung nodules per animal vs 52 in the control. Not significant. -Median control nodules was 2.0, median aerobic control nodules was 0.0. Not significant. |
| Abdalla, 2013 | 23 | 8w old female Balb/c mice |
Mammary / 1mg/ml DMBA p.o. once weekly for 6 weeks |
Forced swimming | 5×|45m|--|8 weeks Water temperature 30+/−4°C |
Same as tumor initiation | -EX ↓ tumor incidence |
| Sáez Mdel, 2007 |
34 | 50d old female Sprague- Dawley rats |
Mammary / 5mg/w DMBA gastric intubation for 4w |
Forced swimming | 30m/d, 5d/w for 38–65d. | 1d after appearance of first tumor |
-No difference in survival time or tumor multiplicity |
EX = exercise or activity groups; SED = Sedentary controls; NMU = nitrosomethylurea; MNU= 1-methyl-1-nitrosourea; AOM= azoxymethane; DMBA= 7,12-dimethylbenz(a)anthracene; DMH= 1,2-dimethylhydrazine; 3’-Me-DAB= 3’-methyl-4-dimethylaminoazobenzene; Fe-NTA= ferric nitrilotriacetate; s.c.= sub-cutaneous; i.v.= intravenous