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Information obtained from animal models (mostly mice and rats) has contributed substantially to the development of treatments for human cancers. However, important interspecies differences have to be taken into account when considering the mechanisms of cancer development and extrapolating the results from mice to humans. Comparative studies of cancer in humans and animal models mostly focus on genetic factors. This review discusses the bio-epidemiological aspects of cancer manifestation in humans and rodents that have been underrepresented in the literature.

It is often difficult to determine the cause of early or sporadic deaths in toxicity studies or animal experiments. To help in the interpretation of early deaths, it is critical that the background incidence of factors contributory to death be recorded and archived. Information was collected from the control groups of 20 carcinogenicity studies using Sprague-Dawley (SD) rats. From a total of 1284 males and 1264 females, 46 male (3.58%) and 44 female (3.48%) decedents were recorded during the first 50 weeks of study. There was no difference between the sexes in the probability of survival. The factors contributory to death were neoplastic in 17 males (37%) and 35 females (79.5%), non-neoplastic in 12 males (26.1%) and 3 females (6.8%) and unknown in 17 males (37%) and 6 females (13.6%). Of the neoplastic lesions, pituitary adenoma and mammary tumours in females were most common, followed by malignant lymphoma and brain tumours in both sexes. Some interesting and comparatively rare tumours were also seen. Death due to non-neoplastic lesions was most often associated with lesions of the urogenital tract, liver and skin. A small number of animals died due to trauma or anaesthetic accident, or were killed because of poditis. A comparatively large proportion of decedents were found dead without any determinable cause of death. This report is intended to be of use to toxicologic pathologists in assessing factors contributory to death in young rats in short-term studies, and more especially to provide a reference to the background profiles of tumour in such animals.

It is sometimes difficult to assess the relevance of tumors that occur in treated animals in short-term studies. This report is intended to establish a general profile of tumor occurrence in young control CD-1 mice and Sprague-Dawley rats. Data from 20 rat and 20 mouse carcinogenicity studies conducted between 1990 and 2002 at Huntingdon Life Sciences, UK. were collected and evaluated. The route of administration was either dietary oral gavage, and the analysis was confined to sporadic deaths (decedents) in control groups occurring during the first 50 weeks of study. In addition, tumor occurrence between 50-80 weeks were compared. In mice, the most common tumor was lymphoma, followed by bronchiolo-alveolar adenoma. In rats, the most common tumor was adenoma of the pituitary gland, followed by mammary fibroadenoma, and adenocarcinoma. When studies of up to 50 weeks, between 50 and 80 weeks, and at 2-year termination were compared, there was no great difference in tumor occurrence except in male rats, in which the most common tumor up to 50 weeks on study was lymphoma, whereas the most common tumor between 50-80 weeks and at 2 years was pituitary adenoma.

Ad libitum-fed (AL) and food-restricted (FR) Fischer-344 male and female rats were monitored for survival, body weight, and spontaneous neoplasms. Mean and maximal lifespans for each group were inversely related to mean body weights. AL males were the shortest lived (mean lifespan 101 wk) followed by AL females (118 wk), FR males (125 wk), and FR females (132 wk). Gross and microscopic examinations were performed on 851 rats from cross-sectional and longevity components of the study. In FR groups, the incidence of mammary gland fibroadenomas, testicular interstitial cell tumors, and pituitary neoplasms was decreased while the latency of these neoplasms was increased. In longevity components, most FR groups had a higher incidence of leukemia than AL cohorts, but all FR groups had a higher mean age at death for the rats with leukemia. Higher leukemia rate in the FR groups was thought to be a result of their extended mean lifespan.

Three separate control lifetime studies were conducted with untreated Crl:CD-1 (ICR)BR mice using a total of 400 mice/sex maintained to 21 mo of age. Similar husbandry practices and environmental conditions were used for all 3 studies. It was noted after study initiation that the Charles River breeding facility of origin was different for each study. The aggregate range of survival and incidence of neoplasms for the combined studies was similar to that previously reported. However, these 3 groups of mice had prominent variation in survival and in the incidence of pulmonary adenomas and systemic amyloidosis in males and females, and in the incidence of hepatocellular neoplasms in males. The present studies indicate that consistent procurement of test animals is an additional variable to be considered in the establishment of a valid database within a test facility when using an outbred mouse.

The most frequently observed neoplasm in 2376 nontreated control female BALB/cSTCrlfC3H/Nctr mice examined at intervals up to 1001 days was reticulum cell sarcoma. It was also the primary cause of morbidity and death. Other frequently observed neoplasms were uterine polyps, alveolar cell neoplasms, Harderian gland neoplasms and lymphomas. Neoplasms, which had a low incidence, generally occurred in the older animals.

The aim of this investigation was to examine the time relationship of the rate of development of spontaneous tumours in the rat, strain CHBB: THOM (SPF). The rats were divided into 6 groups, each of which consisted of 100 male and 100 female animals. The first group was killed at the age of 15 months, and the last group when aged 2 1/2 years. Thus the time interval between sacrificing the individual groups was 3 months. Spontaneous tumours seldom appear in animals up to 15 months of age except in the testes, pituitary and mammary glands. Apart from these organs tumours develop mainly in the lung, lymph nodes, thymus, adrenal cortex, thyroid, ovary, uterus, skin and in the brain. Benign tumours predominate. Malignant tumours with metastases are rare. The incidence of tumour formation increases after the age 21 months. Statistically significant increases can only be shown in a few organs.

The paper discusses the incidence of spontaneous tumors and general morbidity in albino noninbred rats raised at the N. N. Petrov Research Institute of Oncology of the USSR Ministry of Health and used in different chronic experiments. It was found that spontaneous tumors occur, on the average, in 25.7 and malignancies--in 6.2%. Infectious hemorrhagic pneumonia and gastroenteritis (acute capillary toxicosis) are relatively infrequent. The general morbidity patterns in these rats are similar to those in Wistar line, the essential difference being a lower frequency of tumors of the medullar layer of adrenals. Hence, the rats bred at the Institute may be successfully used in various chronic experiments, including those associated with carcinogenic studies.

Data obtained from the 10 year study of the spontaneous neoplasm incidence in mongrel mice and rats (males and females) from the colony of the R.E. Kavetskiĭ Institute for Oncology Problems are adduced. Spontaneous carcinogenesis was at an average 1:8 in mice (132 tumours per 1120 mice) and 1:3 in rats (93 tumours per 335 rats). Tumours of mammary glands and of pituitary prevailed in rat females.

Spontaneous tumors in untreated (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice used as controls in carcinogenicity tests were recorded. In both sexes, the development of spontaneous tumors was age-related. In 244 male mice, the most common tumors were hyperplastic nodules of the liver, hepatocellular carcinomas, malignant lymphomas/leukemias, lung adenomas, and adenocarcinomas. In 246 female mice, the most common tumors were malignant lymphomas/leukemias, pituitary adenomas, neoplastic nodules of the liver, hepatocellular carcinomas, and lung adenomas. Hepatocellular carcinomas metastasized in 20.3% of the animals with these tumors. Few other tumors except malignant lymphomas and leukemias metastasized. Various tumors of other organs and/or tissues were found at low incidences.