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[The changes in the sphingenine/sphinganine ratio in sphingolipids of transplantable rat tumors depends on a transplantation organ].

The content of sphingenine (sphingosine) and sphinganine was determined in the total pool of sphingomyelin and ceramide in the rat tumors transplanted subcutaneously and intrahepatically. The sphingenine/sphinganine ratio in the subcutaneously transplanted sarcoma M1 and cholangiocellular carcinoma RS1 was lower than that in the sphingolipids of the intrahepatically transplanted tumors. However, the sphingenine/sphinganine ratio in the subcutaneously transplanted rat hepatoma 27 was higher than in the intrahepatically transplanted hepatoma. These observations indicate that the sphingenine/sphinganine ratio in sphingolipids of tumors depends on the tumor type and its cellular microenvironment.

Animals↗

Effects of high-fat diet on incidence of spontaneous tumors in Wistar rats.

In a 2.5-year carcinogenicity study, two groups, both including male and female Wistar rats, were fed two different diets with 4% and 16% fat. In addition to 4% soybean oil, the high-fat diet contained 12% mono- and diglycerides, of which 85% was stearic acid and 13% palmitic acid. There was no difference in food consumption, body weight, weight gain, and longevity between the two groups. A statistically significant increase in the incidence of tumors in the high-fat group was seen in fibroadenoma of the mammae (female, p = 0.05). No statistically significant difference was seen when the incidence of benign mammary tumors (adenomas and fibroadenomas) was combined, just as the overall incidence of mammary tumors (adenomas, fibroadenomas, and adenocarcinomas) was not significantly different between the groups. A statistically significant decrease in the incidence of tumors in the high-fat group was seen in adenoma of the parathyroid gland (male, p = 0.04) and medullary carcinoma of the adrenal gland (male, p = 0.04). Combining the incidence of benign and malignant tumors of the adrenal medulla led to a further increase in the level of significance (p = 0.02). The present study showed that a high-fat diet influenced the tumor incidence in certain organs of rats. However, the overall differences in tumor incidence between rats fed the low- and the high-fat diet are considered marginal. Therefore we were not able to confirm or deny the hypothesis that a high-fat diet promotes the development of cancer. It should be noted that, in our study, fat accounted for about 30% of the total energy in the high-fat diet. This is much below the amount of fat normally found in the western diet but corresponds well to the level recommended for human intake. In addition, the rats fed the high-fat diet did not gain more weight, even though no difference was recorded in food consumption (g/kg body wt) between the groups.

Adenofibroma↗

Spontaneous tumors in ACI/N rats.

One hundred ninety-five spontaneous tumors, developing in 55 male and 209 female ACI/N rats in 169 weeks, were studied. The incidence was 56% (31/55) in males and 52% (108/209) in females; their average survival time was 113 and 108 weeks, respectively. These neoplasms were found in all organ systems except those of the sensory and locomotor systems. In the males, interstitial cell tumors of the testis (45.5%, 25/55) were most frequent, followed by those in the adrenal (16.4%, 9/55) and pituitary glands (5.5%, 3/55), skin (5.5%, 3/55), and urinary bladder (3.6%, 2/55). In female rats, tumors of the pituitary gland (21.1%, 44/209), uterus (12.9%, 27/209), mammary gland (11.1%, 23/209), adrenal gland (5.7%, 12/209), urinary bladder (4.8%, 10/209), thymus and lymph nodes (4.3%, 9/209), subcutaneous tissues (1.4%, 3/209), heart (1.4%, 3/209), vagina (1.0%, 2/209), and salivary gland (1.0%, 2/209) were detected. In addition, tumors of the glandular stomach, small intestine, spleen, trachea, lacrymal gland, ovary, brain, kidney, thyroid, and bone marrow were detected in 1 female each, and those of the small intestine, spleen, lung, and peritoneum in 1 male rat each. Only 6 adenocarcinomas of the uterus, 3 lymphatic leukemias, 1 cortical carcinoma, and 1 mesothelioma of 195 tumors observed in the present studies metastasized to remote organs.

Adrenal Gland Neoplasms↗

Effects of age on multiple organ carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl in rats, with particular reference to the prostate.

The effects of age on multi-organ carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) in male F344 rats were examined. Groups of 5-, 35-, and 65-week-old animals were given 4 weekly sc injections of DMAB at a dose of 200 or 150 mg/kg body weight. Prostate carcinomas were induced in 8 to 19% of rats treated, no significant differences in the incidence between different ages being observed. Tumors in the small intestine, skin, pancreas and peritoneum, however, developed more frequently in young than in old animals, whereas higher incidences of testis, preputial and mammary gland lesions were found in the 35- and/or 65-week-old groups. Colon and Zymbal gland carcinogenesis did not reveal any age dependence.

Age Factors↗

A classification of transplantable tumors in Nb rats controlled by estrogen from dormancy to autonomy.

Transplantable tumor lines were previously established from a variety of estrogen-induced tumors in Nb rats, including tumors of the adrenal cervix, salivary gland, and pancreas, a lymphoma, and a liposarcoma. Spontaneous tumors, however, were found to arise in untreated females and showed the same characteristics. Tumor growth was dependent upon or influenced by estrogen when assessed in estrogenized and unconditioned hosts. Intermitten estrogenization was effective, but tumor growth took place more slowly. The type of response observed led to a new classification of five types of hormone-responsive tumors including tumors inhibited by estrogen. Estrogen-dependent tumor cells might remain dormant indefinitely and not grow in unconditioned animals until stimulated to grow by estrogen. The growth rate of hormone-dependent adrenal carcinomas was related to the amount of estrogen. Tumor growth started more rapidly in the presence of low estrogen dose levels in old rats used as hosts than it did in young rats. Breast carcinomas required the largest amount of estrogen for growth, whereas ovarian thecomas would grow in normal females but not in males. The growth rate in conditioned hosts of most transplanted tumors (some have maintained hormone dependency over 10 years) increased over successive generations. Progression, however, towards a more autonomous state after repeated transplantations was remarkably slow, and a sudden change to autonomy was rarely noted. In contrast, transplants of 9,12-dimethylbenz(a)anthracene-induced mammary carcinomas progressed rapidly to autonomy. Fould's concept of progression (2, 3) has been discussed but the described classification of tumors under hormone influence apparently allows a more detailed analysis of definition of different types of progression.

Adrenal Gland Neoplasms↗

[Characteristics of the reproduction of Djungarian hamsters in captivity and spontaneous tumors].

Breeding behavior and fertility of the Djungarian hamster (D. h.) -- Phodopus sungorus campbelli Th-during 8 years (1966-1973) have shown that this hamster species is a suitable laboratory animal. The decline of breeding in winter months, observed in the first years of maintaining D. h. in our laboratory, became less pronounced in the last three years. D. h. seems to be resistant to common infections of laboratory animals. The only infection observed in D. h. was on outbreak of trichophytosis which was successfully liquidated. Spontaneous tumors developed in 130 of 1277 D. h. (10%). Mammary carcinoma, squamous cancer of the skin and lung tumors prevailed. In the recent years, the incidence of mammary carcinoma became higher, whereas the frequency of skin tumors was decreased.

Adenocarcinoma↗

Spontaneous tumor incidence in female brown Norway rats after lifelong diets high and low in linoleic acid.

High linoleic acid (C18:2) (group I; 17.7 cal%) and low C18:2 (group II; 3.3 cal%) diets were given to groups of inbred Brown Norway virgin female rats (100 animals/group), during their whole life-span. A total of 140 tumors were found in group I and 123 tumors in group II; the median survival times of the 2 groups were 124.2 and 118.5 weeks, respectively. Total spontaneous tumor incidence and median survival times were not significantly different. However, significant differences were found in the incidences of some specific tumors: The numbers of reticuloendothelial tumors and adrenocortical carcinomas were significantly higher in the group of animals receiving the low-C18:2 diet. A high incidence of tumor multiplicity, however, resulted in a significantly greater number of mammary tumors in the high-C18:2 diet group.

Adrenal Cortex Neoplasms↗