Lorenzo Tomatis

The effects of multiple and single administration of dimethylnitrosamine to hamsters.

A single treatment with dimethylnitrosamine (DMN) in rats has been reported to induce kidney tumors, in some cases ethmoidal tumors and very few or no liver tumors. The administration of one or three doses of DMN to hamsters results in the induction of liver cell carcinomas and of a few cholangiomatous lesions, and no kidney tumors. Dose and time of administration of DMN play probably a major role in the different carcinogenic responses to DMN observed in rats and hamsters.

INCREASED INCIDENCE OF TUMORS IN F1 AND F2 GENERATIONS FROM PREGNANT MICE INJECTED WITH A POLYCYCLIC HYDROCARBON.

Summary Pregnant Swiss mice were injected i.p. with 500 or 350 γ of 7,12-dimethylbenz(a)anthracene (DMBA) in tri-n-caprylin. Delivery occurred between 12 hours and 7 days after the injection. Five females, descendants from 2 pregnant mice injected with 350 γ of DMBA, were mated with their brothers. In both F1 and F2 untreated descendants a high incidence of tumors occurring at various sites was recorded. The most frequently occurring tumors were mammary carcinomas, granulosa cell tumors of the ovary and lung adenomas in the females, and lung adenomas, adenomas and carcinomas of the paraurethral gland in males. Many of the tumor-bearing animals bore more than one tumor. The transmission of the carcinogen via the mothers milk probably occurs in the mice of the F1 generation. The enhancement of an inherited low susceptibility to certain tumors seems to be the cause for the high incidence of tumors in the mice of the F2 generation.

Subcutaneous Carcinogenesis by 14C and 3H Labelled Polymethylmetacrylate Films

14C and 3H labelled and not labelled polymetylmetacrylate films of various sizes were implanted subcutaneously into Swiss mice. Sizes of 3 mm2 and 6 × 12 mm appeared to posses a borderline carcinogenic activity, which was not influenced by the labelling. Similarly, the carcinogenic activity of the 12 mm2 films was not modified by the 14C or 3H labelling. There was however a notably higher incidence of tumors in a small group of mice implanted with 15 mm2 films labelled with 14C. The rate of excretion of radioactivity in the urine of mice implanted with the labelled films, rose sharply between the 2nd and the 8th week from implantation. It suddenly fell at the 9th week to minimal values. The rise in the excretion rate of radioactivity observed in the first 8 weeks from implantation, has been attributed to the possible presence of residual monomers in the films.

Subcutaneous carcinogenesis by implants and by 7,12-dimethylbenz[a]anthracene.

The effects of the combined administration of urethan or Trypan Blue to the s.c. injection of 7,12-dymethylbenz[a]anthracene (DMBA) were investigated. The repeated administration of Trypan Blue resulted in a marked inhibition of sarcomas arising around Teflon disc implanted s.c. It was thus confirmed, in a different strain of mice, the result of a previous experiment, where Trypan Blue was shown to exert an inhibiting action on the sarcoma production by glass fragments implanted subcutaneously. No consistent inhibiting action of Trypan Blue on the sarcoma production by DMBA could be demonstrated. Urethan administered before, concurrently or at various time after DMBA administration had no apparent effect on the incidence of sarcomas induced by DMBA. In a previous experiment urethan was showed to enhance the incidence of sarcomas arising around Teflon films.

Long Term Culture of Thymic Cells from Newborn Mouse Thymus Fragments.

Summary. In vitro Cultures of newborn mouse thymic cells were followed for as long as 120 days. Depending on the technique of explantation, two distinct types of cell populations were obtained: whereas in cultures derived from thymic fragments embedded in plasma clot the final result was a pure colony of reticulum cells, in cultures derived from unattached thymus fragments the cell population mainly consisted of lymphocytes, monocytoid cells and plasmacytoid lymphocytes.

The presence of lymphocytes in long term cultures of newborn mouse thymic epithelium.

Summary Thymic epithelial cells derived from newborn mouse thymic fragments were cultured in vitro for over 22 months. Subcultures were started by transferring minute cell sheets obtained by mechanical scraping of the original culture when it was 14 months old or older. Lymphocytes, many of them with the morphological appearance of plasma cells, were seen in the subcultures. Intact lymphocytes, as well as mitotic figures were seen within cytoplasmatic vacuoles of the epithelial cells. The possible bearing of these observations on the origin of the thymic lymphocytes is briefly discussed.

Effect of a single application of croton oil in skin carcinogenesis.

Conclusions In our prior studies we had established that a single dose of 200 μg of the carcinogen DMBA is highly effective, giving rise to tumors of the skin in almost 50% of treated Swiss mice, of which a high proportion appear malignant, namely 28% become squamous cell carcinomas (2). A dose of 100 μg of DMBA, on the other hand, is a borderline carcinogen giving rise to a small proportion of papillomas many of which regress and few of which progress to malignancy. This result was confirmed. From other studies it is well known that a dose of 100 μg is an effective initiating dose of this carcinogen for the skin; that is, if it was followed by repeated applications of croton oil or some other promoting stimulus, many tumors would appear(10.11). In the present study this dose of carcinogen was combined with a single application of croton oil at 2 dosages. In no instance did croton oil, thus administered, give rise to any promoting effect, but to the contrary appeared. if anything, to engender a reduction in tumor incidence. This finding applied not only to combinations with the 100 μg dose of DMBA, but also to the 200 μg dose. It thus seems clear that the difference in the carcinogenic capabilities of doses of 100 μg or 200 μg of DMBA cannot be explained on the basis of additional “injury” inflicted by the higher dose, if the “injury” is of the same type as that caused by croton oil. It is clear that the promoting effects of croton oil are quite distinct from the initiating and carcinogenic actions of DMBA since croton oil requires repeated applications to manifest its effect and has, if anything, the reverse effect under the conditions of the present expriment. The qualitative nature of the tumors seen in the croton oil treated groups appears consistent with that observed in many previous studies in that there was a predominance of benign and regressing lesions(2).

Neoplastic conversion in vitro of newborn mouse thymic cells.

Summary Newborn mouse thymic cells were cultured in vitro for over 2 years and their possible malignant conversion was tested by injecting the cultured cells into newborn and adult syngeneic hosts. While no tumors grew in the adults, one tumor grew subcutaneously at the site of injection in 9 of the 40 newborns and in one newborn a tumor grew in the retroperitoneum. All tumors had identical morphological characteristics. Two of the tumors so obtained were transplanted and are at present at the 17th transplant generation.