Tumori Journal

Sprague-Dawley rats, castrated (20) and intact (20) were given orally 10 mg 3-methylcholanthrene 6 times a week for 50 days. Half of the ovariectomized and half of the non-ovariectomized animals were additionally and simultaneously injected with 4 mg of progesterone intramuscularly.

All the rats under experiment developed multiple mammary tumours (adenocarcinomas), except for 4 out of the ten animals castrated and treated with 3-methylcholanthrene. The earliest occurrence was observed in the intact rats treated with 3-methylcholanthrene and progesterone (average time of occurrence of the neoplasms: 40th day of treatment).

The mammary glands of the castrated rats given 3-methylcholanthrene were less atrophic than those of the corresponding controls. Mammary proliferations, of the dioestrus type, were observed in the ovariectomized rats treated with 3-methylcholanthrene and progesterone, and in tre normal rats treated with 3-methylcholanthrene only. In the non-ovariectomized rats, the concomitant administration of 3-methylcholanthrene and progesterone brought about changes similar to those of the first day's pregnancy. The present experiment shows that 3-methylcholanthrene behaves like an oestrogen in stimulating the mammary gland and in inducing breast cancers in the rat. Progesterone acts concomitantly with 3-methylcholanthrene and enhances its activity.

The present paper reports results of a study of cytologic smears obtained from a group of research gynecological patients and is concerned with inflammatory and precancer conditions that show cells with « perinuclear halos ». It is pointed out that the pathological degenerations of the cytoplasm are initially similar to granules, vacuoles, or drops, which later grow and conglomerate, pushing the nucleus to the periphery. In the clear cells the morphological picture is very different: the pale area always surrounds the chromatin, growing from the center to the periphery, and being separated from the cytoplasm by a clearcut membrane. The lesion is thus considered as a « pale turgescence of the nucleus », caused by an acute or chronic irritation, resulting in an alteration of the physicochemical equilibrium between the nucleoplasm and the hyaloplasm. Some considerations in favour of this theory are presented, but future cytochemical and electromicroscopical studies will complete this first morphological finding.

As an introduction to a series of papers on tumor substances inhibiting the activity of liver catalase, a critical review of the present situation of the general problem about the inhibition of this enzyme in tumor-bearing organisms is outlined. Data from researches carried out in order to determine the nature of the inhibitors are then exposed. « Toxohormone » was prepared from, human and experimental tumors and from ascitic fluids. It has been observed that, by the methods usually employed for such preparation, the 90–95 percent of the activity is lost.

Active, very heterogeneous fractions were obtained, by solvent extraction, from « toxohormone ». A globulin fraction from ascitic fluid proved very active; « toxohormone » was prepared also from this fraction but with a loss of 95 percent of the original activity. It is concluded that at least two categories of inhibitors exist, one of proteic nature, and one probably derived from the first, of low molecular weight. For the investigation of such substances, methods less damaging than those employed for « toxohormone » are necessary.

The treatment with 4-chloro-testosterone acetate exerted, in 10 patients bearing malignant tumours or operated upon, a manifest proteoanabolic effect, with increase in the body weight, augmented proteinemia, retention of urea and of the other catabolites of the protein turnover and improvement of the general conditions. No unpleasant side effects were observed.

The action of a new quinoline compound, the 2-Methyl-4-Mercapto-6-Methoxy-Quinoline, on « in vitro » cultures of human cancer cells (strain KB) is described. The substance tested at concentration ranging from 0.1 γ/ml to 100 γ/ml, showed a powerful and specific citotoxic action at concentrations higher than 1 γ/ml.

The action exerted by the 6-aminonicotamide (an antivitamine considered as a possible antitumoral drug) on some biochemical processes of the cell has been studied. Results are exposed, which demonstrate that the 6-aminonicotamide is able to produce an elective denaturation at the level of some enzyme activities which are involved in glycolytic processes. The enzymatic impoverishment brought about by this substance was found to be especially marked in the spleen tissue. This finding is a further demonstration of the elective antilymphatic activity characteristic of this antivitamine.

The behaviour of lymphoid and epithelial tissues of the tonsil has been studied in rabbits treated with three substances supposed to have antiblastic activity: the 6-aminonicotamide, the dimethyl-dimetansulfonyloxybutane and the enanthic aldehyde. A marked action on the lymphoid tissue was exerted by the first substance, which nearly failed to act on the epithelium; no changes at the level of both tissues were induced by the second, and a cytolytic activity on the epithelium by the third one.

A histological investigation has been carried out on 30 radiodermitic lesions (late lesions, chronic radiodermitis, cancerized radionecroses). Changes of hypertrophic and degenerative type, never described before, have ben shown in the Pacini's corpuscles. They may be ascribable to the action of the ionizing radiations and have a significant role in the pathogenesis and intensity of the early pain which occurs in radiodermitis.

The DNA modifications in medullary granuloblasts have been studied as « direct » effect as well as « indirect » or late effect of X-rays. For the purpose rabbits have been irradiated « in toto » after lead screening of two limbs. The modifications, consisting in a DNA increase, are cytologically expressed in the formation of giant cells, and have been obtained both as direct and indirect effect of X-rays.

These results, if considered as a biochemical and cytologic aspect of the carcinogenic action of radiation, constitute an experimental demonstration that this carcinogenic action must be looked upon also as an « indirect » or « late » effect.