Jacob Furth

Direct determinations of plasma, cell, and organ-blood volumes in normal and hypervolemic mice.

Summary Direct single and combined cell- and plasma-volume determinations were made on normal and polycythemic mice with 32P-tagged red cells and 131I-tagged plasma. The data indicate that: (a) The Evans-blue plasma volumes in mice are above the probably more correct 131I-plasma volumes by a factor of 1.2 and in rabbits by a factor of 1.08. (b) The so-called mixing time of Evans blue is a withdrawal time of this dye by Evans blue-affin cells, most of which are probably macrophages. (c) The cell volume calculations based on Evans-blue values are higher than those obtained by direct determinations with the 32P technic by a factor of 1.56 in normal and 1.51 in tumor-bearing mice tested. (d) The average body hematocrit in mice is approximately 0.88 times the venous hematocrit. (e) On the basis of these conversion values a calculation of all values can be made if only one technic is employed (Fig. 1). (f) Hypervolemia caused by estrogen-secreting tumors is attributable to an almost selective plasma-volume rise while that with luteoma is due primarily to polycythemia and, to a lesser extent, to a plasma volume rise. The valuable counsel of Dr. C. W. Sheppard is gratefully acknowledged. Miss Mary M. Knoohuizen and Miss Maryann Huddleston assisted in this work.

Transplantable mastocytoma in the mouse containing histamine, heparin, 5-hydroxytryptamine.

Summary 1. A transplantable mastocytoma of the mouseis described. The tumor is benign and composed of cells indistinguishable from normal mast cells. 2. It contains greater quantities of histamine and heparin than have previously been found in normal or tumorous mast cells. It also contains large amounts of 5-hydroxytryptamine.

Some late effects in mice of ionizing radiation from an experimental nuclear detonation.

The first experimental investigation of the late effects of ionizing radiations from a nuclear detonation in a very large population of mammals (mice) was planned with great care by a team of investigators of the Atomic Energy Commission and the Armed Forces. The animals were placed at various distances from the hypocenter, and the intensity of exposure was monitored by both physical and biological methods. The mice were of the genetically uniform LAF1 strain, of both sexes, and six to twelve weeks of age when exposed. After the early mortality rates had been recorded, the animals were transported to Oak Ridge, where they remained individually caged, the cages randomized in one large animal room, until natural death. Sick animals were killed in extremis. The radiations from the nuclear detonation were composed predominantly of high-energy gamma rays, with a small component of fast and a still smaller component of slow neutrons, the gammaneutron ratios increasing with the distance from ground zero. The par...

The Relative Biological Effectiveness of Neutrons, X-Rays, and Gamma Rays for the Production of Lens Opacities: Observations on Mice, Rats, Guinea-Pigs, and Rabbits

The relatively high radiosensitivity of the lens of the eye to neutron radiation is now well established (Evans, 1948; Ham, 1953). In addition to experimental cataracts obtained in several species of neutron-irradiated laboratory animals, lens opacities have been observed in human beings exposed to cyclotron neutrons (Abelson and Kruger, 1949; Dollfus, 1950; Krause and Bond, 1951) and to fission neutrons from atomic detonations (Cogan et al., 1949; Sinskey, 1955). The growing prevalence in our environment of neutron sources such as high-voltage generators (cyclotrons) and reactors makes it increasingly important to know how much neutron radiation the human lens can tolerate. Furthermore, if neutrons are more effective than electromagnetic waves in causing lens opacities, precise comparison of the cataractogenic effects of these radiations should be made to further the knowledge of their fundamental radiobiologic differences. This investigation was undertaken in an attempt to obtain quantitative informatio...

Hormones as Etiological Agents in Neoplasia

The hormonal concept of carcinogenesis was initiated by the intuitive studies of Beatson (1896) on the relation of breast cancer to the ovary. Epidemiological studies of mammary tumors of highly inbred strains of mice led Bittner and his associates (Bittner, 1946–1947) to the recognition of genetic, viral, and hormonal components in the development of breast cancer. Independently, Rous and Kidd (1941), on the basis of experimental studies on induction of skin cancers with carcinogens, advanced the multifactorial concept of tumorigenesis and postulated the existence of latent cancer cells. The recognition of “progression” during the course of neoplastic disease was best conceived by Foulds (cf. 1969). Finally, the recognition of immunosurveillance (Burnet, 1970; Jerne, 1973; Klein, 1973–1974) and of immunological and hormonal factors capable of restraining or enhancing tumor growth completed the picture of the complexity of forces involved in initiation and growth of tumors. The last of these—hormones—is reviewed here in light of all other forces.

ACTH Secreting Transplantable Pituitary Tumors.

Summary and Conclusions Two pituitary tumors occurring in mice exposed to ionizing irradiation proved readily transplantable causing in the recipients obesity with thymic atrophy, hyperglycemia, polyuria, sometimes with glycosuria, severe lymphocytopenia, and hypertrophy of the adrenal cortex. On the basis of these findings it is concluded that this tumor secretes ACTH. There is lack of evidence of stimulation of any endocrine organ other than the adrenal.

Relation of Mammotropes to Mammary Tumors. IV. Development of Highly Hormone Dependent Mammary Tumors.

Summary 1. Highly hormone dependent mammary tumors were induced in rats by a combined treatment of a subthreshold dose of 3-methylcholanthrene and mammotropic hormone(s) (administered by grafts of a functional mammotropic tumor). 2. Growth of these mammary tumors was dependent upon continuation of stimulation by mammotropic hormone(s). 3. Grafts of the mammary tumors remained latent up to 262 days, growing only after mammotropic hormone(s) was administered. 4. Upon resection of mammotropic tumor, a primary mammary tumor promptly and completely regressed; 5 other primary tumors in rats carrying functional mammotropic tumors grew progressively. The authors acknowledge the technical assistance of Mary Campbell.

The Role of Prolactin in Carcinogenesis

Publisher Summary This chapter discusses the role of prolactin in mammary carcinogenesis. Prolactin plays a major role in mammary carcinogenesis on a par with its natural inducer, estrogen. There are still numerous dark areas concerning carcinogenesis by both of these hormones. Their role is regulation of growth and function of the mammary gland, aided by several other hormones. Estrogens can be directly carcinogenic as it is capable of changing the genetic code. Natural estrogens have a structural homology with carcinogenic polycyclic hydrocarbons and are physiologically led to the nucleus complexed with their cytoplasmic receptors. However, the nonsteroidal estrogenic diethylstilbestrol (DES) seems to be also carcinogenic. Prolactin acts on the plasma membrane, where its instructions for growth and function of the mammary epithelium are carried out by the “second messenger,” cyclic 3′,5′-adenosine monophosphate (cAMP). Estrogen is a “cosmopolitan” hormone— that is, it has receptor sites in many cells, in addition to the mammotrope of the pituitary.

Relation of Mammary Tumors to Mammotropes.∗ H. Hormone Responsiveness of 3-methylcholanthrene Induced Mammary Carcinomas

Summary 1. About 72% of primary 3-MCA induced mammary carcinomas were inhibited to varying degrees by ovariectomy and 86% by hypophysectomy. 2. Most inhibited tumors remained minute; a few resumed progressive growth and a moderate number (about 37% in the hypophysectomized series) could not be identified at autopsy. 3. Grafts of functional mammotropic tumors (providing a steady supply of mammotropin) on hypophysectomized animals, whose mammary tumors have markedly decreased in size following ovariectomy or hypophysectomy, caused not only resumption of progressive tumor growth, but also appearance of numerous new mammary tumors. Thus MtH can unfold latent neoplastic potentialities.

Relation of Mammary Tumors to Mammotropes. I. Induction of Mammary Tumors in Rats

Summary 1. Mammary carcinomas occurred in 50% to 100% of 64 F/Fu female rats surviving 90 to 96 days after initiation of intragastric instillation of 3-MCA twice weekly in 10 mg doses, and all of 18 W/Fu rats similarly treated, after 72 days of treatment. In castrated F/Fu male rats similarly treated, no mammary carcinomas developed. 2. Squamous carcinomas arising in periauricular sebaceous glands developed in about one half of both male and female F/Fu rats surviving 123 days, and in none of the W/Fu rats. Similarly, squamous carcinomas of skin and oral mucosa occurred in approximately 12% of F/Fu rats of both sexes and none in W/Fu rats. 3. Leukemias, including lymphoma (about 9%) developed in F/Fu rats and none in W/Fu rats. 4. A single dose of 3-MCA or MtH alone failed to produce mammary carcinomas in 8 W/Fu rats, while 6 of 7 rats receiving both, developed mammary carcinomas.