M. Janowski

Multiple target cells type for infection by RadLV(Rs), a radiation leukemia derived virus

In order to determine which cell type is susceptible to RadLV(Rs) infection, cell suspensions from different tissues were cultured in diffusion chambers (DC) in the presence of viral extracts and tested thereafter in vivo for a leukemogenic activity. Several experiments have clearly shown that neither passive entrapment of the virus nor spontaneous cell transformation occurred to a significant extent in the DC. This was demonstrated not only with RadLV(Rs) but also with Rauscher Leukemia virus (RLV), a much more potent oncogenic virus. Whereas spleen, bone marrow and thymus cell suspensions were susceptible to RadLV(Rs) infection in DC, only spleen and bone marrow could be infected by RLV. In the case of RadLV(Rs), cell suspensions devoid of T derived lymphocytes or deprived of surface immunoglobulins (Ig) remained able to propagate the disease. Moreover, the sera of the recipient mice injected with DC cultured cells contained increased concentrations of IgG1, IgG2a, IgG2b, IgA and IgM. This denotes a polyclonal stimulation of B derived lymphocyes similar to that occurring after the in vivo administration of acellular extracts. The cells infected in DC with RadLV(Rs) were tumorigenic in the recipient mouse not by their own multiplication but by virus production. This was demonstrated by firstly, syncitia formation of XC cells by direct co-cultivation with DC cells; secondly, leukemia induction by cell free extracts prepared from the DC content; thirdly, absence of multiplication of DC infected cells from C57B1/Rb (6;15) 1 Ald mice (38 chromosomes) after injection in 40 chromosome recipients.

Effect of X rays alone or combined with diethylnitrosamine on tumor induction in infant mouse liver.

The possible combined effects of the initiator diethylnitrosamine (DEN) with X rays on cancer induction in C57BL/Cnb mouse liver were evaluated. Four groups of infant mice were treated as follows: with DEN alone, with X rays alone, with DEN + X rays, and with X rays + DEN. Mice in each group were killed at 10-week intervals over 70 weeks. The following parameters were measured: body weight, liver weight, number and size of macroscopic liver lesions, and number and total surface of the different types of microscopic liver lesions. The number of induced liver foci and carcinomas was found to depend essentially on the dose of DEN. X irradiation did not produce any combined effect on the induction of foci and carcinomas when given 7 days before or after DEN administration.

Effect of X-rays Alone or Combined with Diethylnitrosamine on Cancer Induction in Mouse Liver

The possible combined effects of the initiator diethylnitrosamine (DEN) with X-rays on cancer induction in infant C57BL/Cnb mice were evaluated. Preliminary data show that a dose of X-rays administered 7 days before a single injection of DEN was more effective in inducing liver nodules than when administered 7 days after DEN administration.

Surface proteins of radiation-induced and radiation leukemia virus-induced thymic lymphosarcomas in mice

Thymic lymphosarcomas (TLS) were induced in C57BL mice by X-rays or by Radiation Leukemia Virus (RadLV) and their surface glycoproteins (gps) compared after cell-surface radioiodination and polyacrylamide gel electrophoresis (SDS-PAGE). All lymphocytic antigens tested (T200, 170/100, Thy-1) and proteins with apparent molecular weight (Mr) around 120,000 and 100,000 were present on all tumours, as well as retrovirus--encoded proteins but considerable variation in the Mr of several serologically-related proteins was observed. Therefore, the TLS in C57BL mice form a heterogeneous group, suggesting that T cells can be transformed at different stages of maturation. The possibility that transformation allows or even triggers differentiation is also entertained.

Failure to detect immune deficiency in rats after prenatal or early postnatal irradiation.

We have looked for medium-term sequelae in the immune system of rats that had been X-irradiated (0-2 Gy whole-body irradiation) during prenatal or early postnatal life. At an age of 8 weeks the histology of the spleen was normal, and so was the distribution of B and T lymphocytes. The serum immunoglobulin levels were not significantly altered, even when the different isotypes were considered. At an age of 10 weeks, the rats were immunized with a T-dependent or a T-independent dinitrophenylated-carrier antigen. Normal levels of specific antibodies were generated in all groups of animals injected with the T-independent antigen. The T-dependent response, in contrast, was higher in animals irradiated between day 6 and day 20 of gestation (but not in rats irradiated early after birth). This increase, however, was significant only for the IgM and IgG1 responses of some irradiated groups. Thus no medium-term immunodeficiency could be documented with the methods used. The alteration in a T-dependent response, however, points to a radiosensitive T regulatory mechanism.

Effect of neutrons alone or combined with diethylnitrosamine on tumor induction in the livers of infant C57BL mice

The possible combined effects of the initiator diethylnitrosamine (DEN)+neutrons on the induction of foci, adenomas and carcinomas in the livers of C57BL/Cnb mice were evaluated. Four groups of infant mice were treated as follows: DEN alone, neutrons alone, DEN followed by neutrons and neutrons followed by DEN. Ten mice in each group were killed at 10-week intervals over 70 weeks. The following parameters were measured: body weight, liver weight, number and size of superficial macroscopic liver lesions, and number and total surface area of the different types of microscopic liver lesions. The rate of appearance of foci increased significantly at different times when a dose of 0.125 Gy of neutrons was administered 7 days before or after a dose of 1.25 micrograms of DEN. No significant differences were observed in the total surface area of foci and/or adenomas and carcinomas when increasing doses of neutrons were given 7 days before or after the administration of 1.25 and 2.5 micrograms of DEN.

Assay of tetramisole in immune-depressed mice

SummaryMice injected with a Radiation Leukemia Virus, vaccinated against the Rauscher leukemia, or irradiated under various conditions, were subjected to Tetramisole treatment in order to demonstrate an eventual increase of their immunological potential. Doses between 0.4–250 μg per injection, and various routes and timing of administration were tested. In order to assess various parameters of the immune system, the following factors were taken into consideration: survival, spleen weight, immunoglobulin level, humoral immune response, antibodies against viral glycoprotein, leukocyte migration test and phagocytosis. The results obtained with these tests did not demonstrate a definite adjuvant effect of Tetramisole.