This article is from the WSSF 2008 AFRMA Rat & Mouse Tales news-magazine.

From a member, e-mail
Q We had a person who adopted from us call asking about advice on tumors. She adopted two girls from us about 1½ years ago and one of the girls had a tumor removed and was fine but now both girls have tumors.

These girls are from two different lines.

It seems bizarre to me that both girls would get tumors at the same time. My question is . . . can what they eat cause the tumors? I asked what she was feeding them and they eat a seed mix from the pet store! YUCK! That is one of the first things we tell people not to feed their rats.

After dealing with our last girl who had a tumor removed and died anyway, I am so tempted to completely cut out any lines that have tumors even remotely in them. We have not dealt with them other than with one rat and the old pet store rat who eventually died from old age. We just got some new rats and were informed that two of their relatives had gotten tumors so I don’t even want to use those rats for breeding.

We offered to take both girls back but she is going to have them euthanized. How sad.

Anyway . . . what do you think?

Answer by Karen Robbins
A Yes, diet is a key component in whether or not some rats get tumors. Since the way rats eat seed mixes—picking and choosing—they are not getting a balanced diet which not only can cause tumors but obesity as well. If you keep rats from the same litters and they never have any problems, then I would say the way the sold ones have been fed is probably the cause. They may have also been fed a lot of bad treats as well to add to the problem. You also have to take into consideration other environmental factors such as smoking around the rats, air fresheners/deodorizers/fragrance sprays used, cleaning products used in the home and to clean the cages/hammocks/toys/etc., the drinking water used (tap vs. filtered), type of bedding used in the cage, etc. If rats get tumors, most don’t get them until around the 1½ to 2 years of age. If they get them sooner (1 year or less), then you should look into genetics as a probable cause.

Some people will read on the Internet someone’s opinion about lab blocks being “boring” and not very exciting for rats and seed mixes are better and think that is what they should be doing rather than what the breeder told them to do. It has been known for years that rats are like people and will eat what they like¹, not what is good for them so if given the choice of something healthy vs. sugerysweet/fattening, they will go for the junk. So, it is the owner’s responsibility to feed their pets only good healthy things and maintain a healthy pet that is not overweight.

Mice on the other hand choose healthy things when given the choice. In a study done in 1954², the first things mice will go for are the cereal foods such as rolled oats, oatmeal, whole and ground rice, macaroni, and vermicelli. Next choices were substances containing fats and proteins such as meats, butter, wax, etc. Last choices were sugar, chocolate, and a variety of dried fruits and preserves. The literature said mice avoid legumes even when other food was scarce. The researchers found rolled oats mixed with 20% olive oil to be particularly attractive to mice.

Unfortunately, people keep “humanizing” their pets, so they go to the pet shops and buy the “pretty” packaged, colorful food/products rather than giving something healthy like lab blocks and fresh veggies which is better for the pet.

You might want to consider adding to your adoption application “What kind of bedding do/will you use,” “What kind of food do/will you use,” and “What kind of snacks/treats do you give” just to get an idea of what they currently feed/have fed/plan to feed their rats. Some people just need educating on what is the best food and treats to feed rats. You might want to offer for them to come get their lab blocks from you every month/every other month, that way you will know they are feeding a better diet. Others you can’t convince and those you might consider not adopting to in the future.

Since you have only had two rats with tumors, it doesn’t really sound like a serious genetic issue that you need to cut out the lines (unless the breeders of your one rat are having issues with any of that lineage). With the small number of animals involved, it is hard to know if the number of tumors and number of animals affected is in excess of background or due to a genetic mutation that predisposed to increased tumors. With the new rats you brought in that recently came up with tumor problems in the females in their background, if you do breed them, you will need to keep an eye on all the offspring to see if they develop tumors at an earlier age or more tumors. If they do, that would show the tumor problem is being passed down and that line may need to be stopped.

Most tumors in female rats are benign fiberous mammery tumors (mammary fibroadenoma). If the rat is too old or has breathing issues and can’t be operated on, as long as the tumor isn’t diminishing the quality of the life or causing excessive weight loss or the tumor ulcerates (loses the overlying skin), most rats do fine. Once the effects of the tumor are compromising the quality of the rat’s life, then it is time to consider euthanasia for humane reasons.

There are lots of research papers on tumor prevention, but a couple I found interesting are the following: one paper that says whole apples equivalent to the human consumption of 1, 3, and 6 apples, prevent mammary tumors in rats³; another paper shows raw soybeans rich in protease inhibitors reduce the incidence of mammary tumors in x- irradiated rats⁴. However, breeding rats should not be fed soybeans or soybean products (such as tofu, some infant formulas) as the chemical genistein in soy affects their male offspring’s reproductive organs and reproductive behavior⁵.

An interesting note regarding mice and tumors, in the book The Care and Breeding of Laboratory Animals it tells about tumors in mice possibly being suppressed or eliminated by keeping 10 or more mice together. Also, that mice undergo physiological changes when shipped long distances to a different destination from where they were raised. This influences the incidence of spontaneous tumors in some of the mice to where tumor-prone mice did not develop them after shipment but several generations later in their new home, the tumors gradually came back.

References

1. Raising Laboratory Animals, A handbook for Biological and Behavioral Research, James Silvan, 1966. The Natural History Press, Garden City, New York. ISBN-10: 0385017006.
2. Biology of the Laboratory Mouse, by the staff of the Jackson Laboratory, Earl L. Green, Editor, Second Edition, Dover Publications, Inc., New York, 1966. ISBN 0-486-63185-0. http://www.informatics.jax.org/greenbook/
3. Rui Hai Liu, Jiaren Liu, and Bingqing Chen. “Apples Prevent Mammary Tumors in Rats.” J. Agric. Food Chem., 2005, 53, (6), pp 2341–2343. http://pubs.acs.org/doi/abs/10.1021/jf058010c?cookieSet=1
4. Troll et al. “Soybean diet lowers breast tumor incidence in irradiated rats.” Carcinogenesis.1980; 1: 469–472. http://carcin.oxfordjournals.org/content/1/6/469.abstract
5. Johns Hopkins Medical Institutions (2003, March 11). “Chemical In Soy Alters Reproductive Organs In Male Rats.” Science Daily, www.sciencedaily.com/releases/2003/03/030311074418.htm.

The Care and Breeding of Laboratory Animals, Edmond J. Farris, Editor, 1950, John Wiley & Sons, Inc., New York. ISBN-10: 0471256080.

Answer by Carmen Jane Booth, D.V.M., Ph.D.
A As part of my work as a veterinary pathologist, I frequently have to determine if the number or age at which a particular group of mice develop tumors is related to a specific genetic alteration that may affect a gene related to tumor suppression, or some other as of yet unknown function. Because of this I have read many different research studies and books on the neoplastic and non-neoplastic pathologic changes in different inbred, outbred, and genetically altered strains of mice.

One of the books that I use for rats, involves the pathology of the Fischer 344 strain of rats.

First of all, it is not unusual that both rats developed tumors at the same age. In rodents, the occurrence of some tumors is common for males and females and the number of tumors increases with age.

There are other studies, but I have this one from the rat pathology book that I have the greatest familiarity.

Chapter 35. Tumor incidences in Fisher 344 Rats: National Toxicology Program Historical Data by JK Haseman, J Arnold, SL Eustis pp 555-564 in Pathology of the Fischer Rat Reference and Atlas 1990 by Academic Press, Inc., GA Boorman et al.

They aged rats to 2 years of age. Control (untreated) rats: 1,983 Female, 1,936 Male. The rats were fed ad libitum.

The following are the most frequent tumors by sex:

Most common tumors for males:

Testis: Interstitial Cell Tumor
Pituitary: Adenoma
Mononuclear Cell Leukemia
Adrenal Gland Medulla: Pheochromocytoma

Most common tumors for females:

Pituitary: Adenoma
Mammary Gland: Fibroadenoma
Mononuclear Cell Leukemia
Uterus: Endometrial Stromal Polyp

Over the years I have read papers and it is known that in rats that are spayed or neutered, the incidence of tumors—pituitary, mammary, and testicular (for obvious reason)—decrease.

So how does diet influence the incidence of tumors? I did a literature search on PUBMED on: Affect of diet on the incidence of tumors in rats. Regardless of whether one is for or against the use of rats in research, the fact is that rats are a key animal model for studying the tumor development, new drug development, food, dietary supplements, etc., and there are numerous research papers —I read ~50 abstracts. There was nothing newer than what was reported in the late 1980s. I had the privilege of studying rodent pathology informally while I was working in industry with one of the top mouse (rodent) veterinary pathologists who contributed to the body of work on caloric restriction and tumor incidence in rats and mice. It was through looking at his study slides that I ultimately decided to change my career path from clinical laboratory animal medicine and anti-cancer research to veterinary pathology with an emphasis on mouse pathology.

The most profound dietary effect of age of onset and number of tumors in rats and mice is caloric restriction and feeding a diet low in fat. Obese rats have more tumors and shorter life span than calorie restricted rats.

The comparison is for ad libitum (AL) where the food is always available verses dietary restricted (DR) where the rats are only allowed a percentage of what an AL fed rat would eat that day.

It is known that AL overfed sedentary laboratory rodents suffer from an early onset of degenerative disease and diet-related tumors that lead to poor survival. There is a significant correlation between average food (calorie) consumption, adult body weight, and survival in rats. The use of moderate DR in rodents results in a lower incidence or delayed onset of spontaneous diseases and tumors. In addition, moderate DR significantly improves survival, decreases adult body weight (decreased obesity), and reduces age-related renal, endocrine, and cardiac diseases. A moderate DR regimen of 70–75% of the maximum unrestricted AL food intake is what many of the studies recommended in addition to a nutritionally intelligent diet low in fat.

There are a lot of papers about foods with antioxidants that may or do prevent cancer; however, nothing comes close as diet restriction.

Does what the rats are fed (other than a low fat diet or DR diet) affect their survival and tumor incidence? This is not as clear and I could not find any papers that fit this question precisely. Because of the short life span of rats, they are more sensitive to the effects of carcinogens or toxins in their diet, which is why they are used for carcinogenesis studies. So, the assumption is that the fewer carcinogens, toxins, pesticides, etc., they consume, the lower the incidence of tumors over the background level of tumors due to genetics and other factors.

So, I agree with Karen in that a healthy diet is going to be better than one high in fats and junk. Seed diets alone are not the best. A good lab block diet supplemented with fresh fruits and vegetables, beans, grains, etc., that is low in fat is ultimately better than one high in fats, chemical compounds, etc. As Karen said as well, environment also plays a role. Rats that live with cigarette smoke, etc., are going to have a shorter life span and increased tumor development just as is seen in people.

References
Keenan KP, Laroque P, Dixit R. “Need for dietary control by caloric restriction in rodent toxicology and carcinogenicity studies.” J Toxicol Environ Health B Crit Rev. 1998 Apr–Jun;1(2):135–48. http://www.tandfonline.com/doi/abs/10.1080/10937409809524548?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed

Duffy PH, Seng JE, Lewis SM, Mayhugh MA, Aidoo A, Hattan DG, Casciano DA, Feuers RJ. “The effects of different levels of dietary restriction on aging and survival in the Sprague-Dawley rat: implications for chronic studies.” Aging (Milano). 2001 Aug;13(4):263–72 http://www.ncbi.nlm.nih.gov/pubmed/11695495

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