Fritz Bischoff

Carcinogenic effects of steroids.

Publisher Summary There are structural similarities between the carcinogenic hydrocarbons and the steroids. Under certain conditions, at least in rodents, steroids might produce carcinogenic effects as dramatic as those of the hydrocarbons. The concept of a normal body constituent functioning as a carcinogen might appear paradoxical. It is under such a circumstance that the areas of contemporary thought regarding the carcinogen and carcinogenesis are challenged. The mechanism of solid state carcinogenesis is conjectural: there might be no carcinogen involved. A chemical carcinogen would have a minimal effective dose and would enhance cancer production with increasing dosage. A weak carcinogen requires the effective dose of a strong carcinogen and might not show increasing tumorigenesis with increasing dosage. A cocarcinogen does not produce cancer by itself but in conjunction with another substance, which is carcinogenic in its own right.

The Urinary Output of Catechol Derivatives Including Adrenaline in Normal Individuals, in Essential Hypertension, and in Myocardial Infarction

Based on Shaws specific test, the adrenaline content of the urine of some normal individuals was considerably higher than has been reported by those using the von Euler technic (adsorption at an alkaline pH, elution and bioassay). One patient with myocardial infarction showed highly significant amounts on four occasions. The marked elevation in the Kroneberg-Schümann catechol ratio for hypertension patients as compared with normals, reported by these authors, was not confirmed by our findings. In three cases of myocardial infarction the ratio was elevated. Our ratios for normals confirm the original work.

The Pharmacodynamics and Toxicology of Steroids and Related Compounds

Publisher Summary The steroid hormones are cyclopenta[a]phenanthrene derivatives. Because hormones by definition function at a target site removed from the site of origin, transport mechanisms for and their different affinities for natural or synthetic steroids contribute to the physiologic response. The origin of the natural steroid and the fate of it and its synthetic analogs are governed by endogenous enzyme systems. The role of the steroid at the receptor site, whether it is physical, resulting from secondary valence effects, or by chemical reactivity, is considered. This chapter discusses the synthetics or natural products that do not have the exact steroid carbon-ring skeleton if they produce physiologic effects akin to those of natural steroids by virtue of required spatial configurations and similar active functional groups. Measurement of steroids in early research relied upon the biologic assay, which remains a final arbiter when different methodological approaches yield different reported values.

The Influence of Irradiation of the Ovaries Upon Estrus and Neoplastic Development in Marsh-Buffalo Mice

Evidence has been produced indicating that the Marsh-Buffalo strain of mice is a stumbling block to any attempt to correlate tendency to development of cancer of the mammary gland with the amount of exogenous estrin required to enhance the incidence of this form of cancer in females or to produce it in males (1, 2, 3). Amounts of estrin which enhance formation of breast tumors in other high-cancer strains of mice fail to do so in either males or females of the Marsh-Buffalo strain. The stimulation of endogenous production of estrogens through the gonadotropins has likewise failed to enhance tumor formation of the mammary gland (3, 4). That the tumor is endocrine-linked is, however, well established by the influence of true or of functional castration, and the possibility remains that the production of cancer is the result of an aberration in the hormonal regulation or the production of abnormal hormonal products. In view of the fact that roentgen irradiation of the ovaries, while destroying the follicular...

Influence of Heptaldehyde Upon the Marsh-Buffalo Adenocarcinoma

Strong (1) studied the influence of heptaldehyde on the growth behavior of spontaneous tumors in mice and dogs, and reported an inhibitory effect upon the growth rate of mouse mammary tumors with gross and histologic alterations, especially liquefaction. Baumann et al (2) studied the influence of heptaldehyde upon a spontaneous mammary adenocarcinoma of strain A mice, an ear tumor induced by ultra-violet light, an epithelial tumor induced by painting with benzpyrene, and a transplantable spindle-cell sarcoma originally induced by benzpyrene. It was found that 2 per cent heptaldehyde in the diet resulted in marked caloric restriction, and that the resulting inhibition in tumor growth could be duplicated by caloric restriction alone. When 0.8 per cent heptaldehyde was fed, food consumption became more nearly normal and tumor growth was unaffected. Clark (3), working with a transplantable spindle-cell sarcoma in rats, found that 1 per cent heptaldehyde in the diet produced a 50 per cent decrease in rate of tumor growth without affecting body weight growth. No effect upon regression or liquefaction was noted. Our report is concerned with the influence of heptaldehyde upon the growth of the spontaneous Marsh-Buffalo adenocarcinoma (mammary mouse tumor). Unpublished data indicate that the growth of this tumor, like that of transplantable tumors, is arrested by caloric restriction and specific nutrient deficiency. In mice maintained exclusively upon starch and lettuce and losing 11 gm. weight in twenty days, tumor growth was completely arrested (data for 10 tumors: 8.5 mm. before, 8.6 mm. after), and when the regime was extended some regressions occurred. Since the Marsh-Buffalo tumor is influenced by caloric and nutrient intake, this factor has been controlled in our experiments with heptaldehyde.

The Influence of Inducing Drastic Changes in Body Metabolism Upon the Growth of Sarcoma 180

The present report is a summary of the effect upon the growth of sarcoma 180 of three substances (dinitrophenol, thyroxin, and so-called growth hormone), which affect the general metabolism in various ways. As measured by the effect upon caloric consumption and gain or loss in body weight, these substances produced in our experiments the following changes: Dinitrophenol: No change in caloric consumption 15 per cent decrease in body weight. Thyroxin: 44 per cent increase in caloric consumption 10 per cent increase in body weight growth. Growth hormone: 10–20 per cent increase in caloric consumption 10 per cent increase in body weight. No marked changes in the behavior of sarcoma 180 were noted under these profound disturbances of the general metabolism, the greatest effect produced being a 40 per cent weight increase in tumor growth. The technic of inoculation, the control of food consumption, and the method of recording tumor data were the same as previously described (1–3) with the exception of three experiments, two dealing with the growth hormone and one with thyroxin. In these, matched tumors arising from the same inoculation were paired and the experiment begun at the time of pairing. This procedure decreases the experimental error.

Relation of the Plasma and Whole Blood CO2 in Cancer

Van Slyke and Sendroy 1 have worked out a line chart for estimating the factor by which whole blood [CO2] is multiplied to obtain plasma or serum [CO2]. This factor is dependent upon the pH, the oxygen capacity and the degree of saturation of the hemoglobin. In the majority of blood analyses presented by these authors, the difference between the observed and calculated value was not over 1 volume per cent. In the values calculated from the data of Peters, Bulger and Eisenman, 2 however, a greater deviation was observed. “The greater variability of these bloods was regarded as due to the fact that they were from a miscellaneous group of hospital patients, many of whom were obviously in very pathological condition.” In studies on the blood chemistry of a series of hopeless cancer patients we determined the data required to calculate the plasma [CO2] from the whole blood [CO2]. The plasma [CO2] was also determined. We are reporting the results because of the abnormal relationship between whole blood and plasma [CO2] observed in several instances. The plasma pH was determined by means of the quinhydrone electrode, by a method (slightly modified) recommended by Cullen. The other data were determined by the Van Slyke-Neil manometric apparatus. We have included analyses of the bloods of several noncancerous individuals. The plasma [CO2] of this group as calculated from the line chart falls well within the error found by Van Slyke and Sendroy. The greatest deviation between the observed and calculated plasma [CO2] is 1.2 volumes per cent. The bloods of 11 hopeless cancer patients were studied. Of these the difference between the observed and calculated plasma [CO2] was abnormally large in 5 cases.