Incidence Of Spontaneous Mammary Tumors Research Articles

Tissue fatty acid changes and tumor incidence in C3H mice ingesting cottonseed oil.

The incidence of spontaneous mammary tumors in C3H mice at 35 wk was higher in mice fed rations containing cottonseed oil than in mice fed fats of comparable fatty acid composition. The time to 50% (T50) incidence was also shorter in the first group. The fatty acid composition of tissue lipids from mice fed the cottonseed oil showed changes indicating the presence of cyclopropene fatty acids-higher levels of saturates and lower oleate/stearate and palmitoleate/palmitate ratios. A possible association between the development of a spontaneous mammary tumor in the C3H mouse and the presence of cyclopropene fatty acids in the cottonseed oil is indicated.

The effect of fat-enriched diet on the incidence of spontaneous mammary tumors in obese mice.

SummaryC3H/HeJ mice show a high incidence of spontaneously occurring mammary tumors. Mice made experimentally obese were observed to have an earlier appearance and a greater incidence of tumors than were the normal-weight mice. A fatenriched diet increased the observed tumor incidence in normal-weight mice to about that of obese mice given a regular diet, while a fat-enriched diet further enhanced the already augmented observed yield of mammary tumors in the obese mice given a regular diet. Statistical analysis supported the dependence of tumor incidence and appearance time on the type of diet. The calories consumed by normal mice on a fat-enriched diet was considerably below that of obese mice on a regular diet, yet produced about the same tumor incidence. A specific effect of the fat-enriched diet is suggested.High caloric diets, particularly those modified to include a high portion of fat, have been reported to promote or enhance the occurrence of several types of tumors in various species of animals (...

Suppressed Development of Mammary Tumorigenesis in R III Mice Treated Neonatally with BCG

SummaryThe effects of Bacillus Calmette Guerin on the development of spontaneous virus induced mammary adenocarcinomas in the mammary tumor prone R III strain of mice was investigated. A single injection of 1 × 106 infectious units of living BCG administered to mice between 3 to 4 weeks of age was found to significantly inhibit the rate of development of mammary adenocarcinoma as compared to control mice receiving a placebo injection of medium only. The incidence of spontaneous mammary tumors was essentially identical in both groups (96 vs 98%). However, mammary tumors developed at a consistently later time in the BCG treated animals as compared to the appearance of tumors in the control mice. Mice injected with BCG during the 2nd and 3rd month of life showed a moderately slower rate of development of tumors as compared to animals injected during the 3rd and 4th weeks of life. The possible role of BCG in nonspecific stimulation of resistance to the tumor virus mediated by immunologic factors seems likely.

Role of Prolactin in Rat Mammary Carcinogenesis: Detection of Carcinogenicity of Low-Dose Carcinogens and of Persisting Dormant Cancer Cells 2

Rats used were W/Fu strain with a reported incidence of spontaneous mammary tumors (MTs) of 17%. Most of these have been benign fibroadenomas in older females. X-ray or fast neutron irradiations were given in subthreshold doses, some as low as 10 rads. Also, low doses (150 mg) of a chemical carcinogen (N-nitroso-N-butylurea; NBU) prolactin (MtH). The prolactin was provided by grafting a syngeneic mammatropic pituitary tumor (MtT.W95 or MtT.W98). Tumors developing at the implantation site were chormophobe adenomas. The latent period of tumor induction decreased after the 4th generation of animal passage of the tumors. In some rats, ovariectomy was done 1 week before X-irradiation. No MT was found in 18 untreated controls during 1 year of observation. No MT developed in 32 rats having only the grafts for 9-12 months. Total-body-X-irradiation with 25 or 50 rads alone elicited no MT for 1 year. Among 27 rats exposed to 200 rads of X-rays 2 developed MT fibroadenomas after 5 and 7 months. The supplemental administration of prolactin greatly increased and accelerated the occurrence of MTs in irradiated rats. Most of these were adenocarcinomas. Ovariectomized rats had fewer MTs than intact females. A correlation was found between dose and MT incidence. The persistence of chemically transformed MT cells was shown by the addition of prolactin several months after NBU therapy. MTs developed in 8 of 10 rats within 3 months after the MTT graft became palpable. All but 1 of these were adenocarcinomas. Apparently there had been no repair or elimination of damaged cells in the dormant state. It is suggested that progressive growth of MTs may depend on the hormonal milieu of the host.

Bioactivity of C3H and RIII Mammary Tumor Viruses in Virgin Female BALB/c Mice: Brief Communication 2

The bioactivities of C3H and RIII mammary tumor virus (MuMTV) in virgin female BALB/c mice differed. The average number of mammary hyperplastic alveolar nodules per mouse after noduligenic tests was 20.1 in BALB/cfC3H and 10.7 in BALB/cfRIII females. Spontaneous mammary tumor incidence after 20 months of observation was 47.5% in BALB/cfC3H and 14.6% in BALB/cfRIII females (P less than 0.01). The frequency of lung metastases in mammary tumor-bearing mice was 63.1% in BALB/cfC3H and 16.6% in BALB/cfRIII females (P less than 0.05), although the clinical duration of mammary tumors was the same. These data demonstrated a lower bioactivity of RIII MuMTV when compared to C3H MuMTV in BALB/c mice and suggested that the causative virus may control all the steps of mouse mammary tumor development, including metastasis.

Selenium and cancer: A review

The essential trace element selenium retards the growth of certain chemically induced tumors in animals. The addition of subtoxic amounts of this element in form of selenite to the supply water lowers the incidence of spontaneous mammary tumors in female C 3H mice significantly without affecting the health and life-span of the animals. Arsenic, a selenium antagonist, administered in form of arsenite in the supply water, also lowers the tumor incidence at dosage levels of 10 ppm, but those animals which develop spontaneous mammary tumors under these conditions demonstrate dramatically enhanced tumor growth rates. The results of initial epidemiological studies suggest that the human cancer mortality is lower in areas providing an adequate dietary intake of selenium as estimated from the selenium content in grains and forage crops in various regions of the United States, or the dietary selenium intakes as calculated from food consumption data in various countries.

Reduced Incidence of Spontaneous Mammary Tumors in C3H/He Mice After Treatment with Polyadenylate-Polyuridylate

The effect of treatment with the double-stranded polynucleotide complex polydenylate with polyuridylate [poly(A) with poly(U)] on tumor development in C3H/He mice was evaluated. Poly(A) with poly(U) was injected in newborn females, and mice were observed for 380 days. During this experimental period 42 percent of treated mice developed tumors, while the incidence in the control group was 63 percent. This difference was statistically significant.

Virus Particles in Placenta and Uterus of RIII/Dm Strain Mice

Recent observation of type C virus particle synthesis in placenta of baboons and in human placenta has focused attention on the possible role of that organ in vertical transmission of oncogenic RNA viruses. Distribution of type C (murine leukemia) and type B (mouse mammary tumor) virus particles in some tissues of mice of strain RIII, a strain with high incidence of spontaneous mammary tumors (70%) and low incidence of spontaneous leukemia (3%) has been extensively studied by electron microscopy. However, their distribution in placenta and uterus of RIII mice has not been investigated so far.

Immunochemical characterization of two major polypeptides from murine mammary tumor virus.

A major murine mammary tumor viral (MMTV) antigen, sl, originally described by Nowinski et al. (1967, 1968, 1971), has been purified from RIII mouse milk MMTV by sequential ion-exchange and gel chromatography. The purified protein with sl antigenic reactivity contains carbohydrate, and has an apparent minimal molecular weight of 52,000. It can be designated as gp52 (sl). Another major MMTV viral protein with a molecular weight of 27,000 has also been isolated, and antisera have been prepared against it. Both MMTV gp52 (sl) and p27 viral polypeptides have been iodinated with (125)I and used in immunoprecipitation and competition assays. The two MMTV proteins differ absolutely from each other and from major mouse type C viral polypeptides in molecular weight, immunological reactivity, and amino acid composition. Purified gp52 (sl) in radioimmunoprecipitation inhibition assays reacted in two distinct patterns. One pattern showed partial displacement of antibody which could be converted to the second, a complete displacement, by heating the antigen, presumably by exposing additional reactive determinants. Biologically, the patterns of major MMTV polypeptide expression in milk correlated with spontaneous mammary tumor incidence in different strains of mice, indicating that the sl antigen is group specific for MMTV or that several mouse strains contain the same virus type.

Relationship of prolactin and growth hormone to mammary function during pregnancy and lactation in the C3H-ST mouse.

SUMMARY The secretion of prolactin and growth hormone (GH) in C3H/St mice, a strain having a high incidence of spontaneous mammary tumours, was studied at intervals throughout pregnancy and lactation. Serum and pituitary concentrations of prolactin and GH were measured by specific, homologous radioimmunoassays. Crude extracts of mouse placentae did not cross-react in these assays, indicating that the assay systems measured prolactin and GH of hypophysial origin. Except for a small, brief rise on day 5, prolactin secretion was low throughout most of pregnancy; the serum concentration of prolactin increased appreciably only near term. During lactation, prolactin in serum averaged from 5 to 10 times basal levels (30–40 ng/ml) until day 15 of lactation, after which the concentration declined. In contrast, GH secretion increased early in pregnancy, the concentration rising both in serum and in the pituitary gland consistently after day 5. The serum concentrations reached 3–10 times basal levels (8–12 ng/ml) between days 10 and 20 of pregnancy. There were successive decreases in serum GH concentration after parturition; the concentration reached basal levels on day 5, but it increased thereafter and was maintained at over three times basal levels for the remainder of lactation. The levels of GH in serum were highly correlated with mammary DNA and RNA contents during pregnancy, while prolactin concentration was more strongly correlated with mammary function during lactation.

Influence of tumor fractions on incidence of spontaneous mammary tumors in C3H/HeJ mice.

SummaryOne to 6 injections of alcohol-soluble, protein-free fractions from a transplantable (dbrB adenocarcinoma in DBA/1 mice) and a spontaneous tumor (from C3H mice) significantly lowered the incidence of spontaneous tumors in virgin female C3H mice, but did not cause significant differences in mean age at which tumors appeared, mean survival time after tumor onset, or mean total survival time.

Incidence of spontaneous mammary tumors in mice with Lithospermum-induced diestrus.

SummaryAbout 400 6-month-old virgin female C3H mice were divided into two groups: one was maintained on a normal diet; the other on an anti-estrous diet of 10-15% Lithospermum. Eighteen months later the latter group had developed half as many spontaneous mammary tumors as the former; however, if the differential mortality observed throughout the experiment is taken into statistical account, the tumor incidence ratio for the total period is 3 for the control, 2 for the experimental group. This reduction in tumor incidence was possibly connected with the Lithospermum-diestrus, but inanition and differential survival factors remain to be more fully evaluated.

The Unusual Occurrence of a High Incidence of Spontaneous Mammary Tumors in the Albany Strain of Rats

Although the spontaneous occurrence of mammary tumors in rats is by no means uncommon, the incidence of 50.9 per cent which we have observed among the females of a small breeding colony during a period of eighteen months is much higher than any we have found reported in the literature. This “endemic” development of tumors in a strain of rats which previously had not shown them, with a coincident progressive decline in fertility, indicates that fundamental changes have taken place in this strain which may be of significance in the study of mammary gland neoplasia. Furthermore, studies now in progress disclose certain abnormalities in the sexual cycles of the female rats of this strain, and in the cytology of the pituitary gland. Some results of the latter studies are given in preliminary form in a later section (page 382) of this report. The present communication is for the purpose of recording, as a basis for subsequent reports, certain general information relating to this strain of rats—to be referred to hereafter as the Albany strain—and to describe the different types of tumors which have appeared spontaneously in animals belonging to it.

Gross and Microscopic Diagnoses in Mouse Tumors at the Site of the Mammary Glands

Among the data reported by the Jackson Memorial Laboratory in 1933 a staff paper appeared that recorded the existence and transmission of extra-chromosomal influence affecting the incidence of spontaneous mammary tumors in mice. In one of the reciprocal outcrosses used in the above and reported in full by Murray and Little (1935 a ), the inbred parent stocks were a dilute brown strain called d, and the C57 black strain called B. Mammary tumors have been almost unknown in the B strain but the d strain has an incidence of 50 per cent mammary tumors in virgin females and about 80 per cent in the breeding females which reach the cancer age. The above outcross data were based upon the gross findings in living animals and include all tumors that by position and physical characteristics were considered to be of mammary gland origin. Nearly 100 per cent of all tumors occurring at this site in the high-mammary-tumor strain d have been either adenomata or carcinomata. Similarly situated new growths in the hybrids were naturally assumed to be tumors in which the epithelial elements were definitely the site of the most pronounced neoplastic development. The object of this paper is to discuss the types of tumors found on histological examination in the hybrids of this reciprocal outcross. In the first generation of the dB cross, with mothers from the high-cancer line and fathers from the low-cancer line, there were 113 virgin females which reached the cancer age. Of these, 45, or 39.82 per cent, developed tumors that grossly were considered to be mammary tumors. Three were lost, 41 were carcinomata, and one was an adenoma. Thus 100 per cent of the tumors that could be diagnosed histologically were of epithelial origin and 97.61 per cent were malignant.