Induction of a rat T cell lymphoma-leukemia by magnesium deficiency--a study of fetal defense against maternal neoplasia.

If Sprague-Dawley rats, 25-30 days old, are fed a diet containing 4-5 mg% of Mg, about 25% of survivors develop a large tumor of the thymus within 6-12 weeks. The tumor is composed of lymphoblasts, which seem to arise from the thymic reticuloendothelial system and, at times, disseminate as an acute T cell lymphoma-leukemia of unknown etiology. If the tumor cells are transmitted intraperitoneally to rats, 14-16 days pregnant, a local invasive and generalized disease is established in the mother but not in the fetuses or their domain. However, if the neoplastic cells are injected into the fetal domain, they colonize the fetal tissues. The colonization by tumor cells is most impressive in the extravascular structure of the placental labyrinth but not in the placental syncytiotrophoblastic zone at the maternal-placental junction. This raises the question as to whether this zone may functionally mediate not only the well-known absolute intrauterine fetal defense against maternal metastatic neoplasia, but also the defense of the fetus against maternal immunologic rejection.

Further evidence for papovavirus as the probable etiology of transmissible lymphoma of Syrian hamsters.

The role of hamster papovavirus as the etiology of transmissible lymphoma was investigated under strict conditions that prevented natural exposure to the lymphoma agent. In an initial experiment, 19 hamsters that were exposed naturally to transmissible lymphoma were placed in direct and indirect contact with weanling hamsters from an uninfected source. Lymphoma developed in the original infected hamsters as well as hamsters maintained in direct and indirect contact. In addition, one of the contact hamsters developed cutaneous epitheliomas, containing hamster papovavirus. Epithelioma homogenate was inoculated into primary hamster embryo cultures, in which hamster papovavirus replicated. Second and third passage tissue culture fluid containing hamster papovavirus induced lymphomas in suckling and weanling hamsters. Cell culture fluid from uninoculated embryo cultures was not oncogenic.

Transmissible lymphoma and simian acquired immunodeficiency syndrome in rhesus monkeys.

Four rhesus monkeys (Macaca mulatta) were inoculated with a homogenate of a cutaneous lepromatous leprosy lesion from a mangabey monkey (Cercocebus atys). One died of B-cell lymphoma, and another died of an immunodeficiency syndrome. Cell suspensions prepared from the tumor and spleen of the monkey with lymphoma induced lymphoma or an immunodeficiency syndrome when inoculated into additional young rhesus monkeys. The immunodeficiency syndrome was similar to simian acquired immunodeficiency syndrome and consisted of opportunistic infections, lymphoid hyperplasia or atrophy, wasting, and syncytial cell formation. Mitogen responses and percentages of T4- and T8-positive lymphocytes were normal until the animals were moribund. Lymphoblastoid cell lines became established in vitro from tumor cell suspensions. These cells were infected with a herpesvirus related to Epstein-Barr virus. In addition, a retrovirus morphologically similar to human T-cell lymphotrophic virus type III (HTLV-III) and simian T-lymphotrophic virus type III (STLV-III) was isolated from one of the lymphoblastoid cell lines (LCL). Type D retroviruses could not be demonstrated in the monkeys in the transmission study; however, a retrovirus similar to that in the LCL was isolated from 4 animals by coculture of peripheral blood lymphocytes with the human cell line H9. These results suggest that this retrovirus, STLV-III/Delta, may be associated with the immunodeficiency syndrome in these macaques and may be of mangabey origin.

Papovavirus in epitheliomas appearing on lymphoma-bearing hamsters: lack of association with horizontally transmitted lymphomas of Syrian hamsters.

Several epizootics of lymphoma occurred in a colony of LVG hamsters contaminated with an unusual, horizontally transmitted, subviral, lymphomagenic agent. Hamsters with horizontally transmitted lymphoma, or others housed with these hamsters, occasionally developed epitheliomas bearing an unclassified papovavirus. The possibility that the virus present in the wart-like structures in our hamster colony could activate lymphoma was tested, and a search was conducted for mature virions in passaged epitheliomas and lymphomas. The agent responsible for the skin epitheliomas in our hamster facility was an icosahedral, 36-nm virion compatible with the morphology of a polyomavirus or simian virus 40. Horizontally transmitted lymphoma cells and epitheliomas contained hamster papovavirus (HaPV) DNA sequences detected by dot hybridization; however, such sequences were not found in extracts of lymphomas with oncogenic potential. In contrast to reports by other investigators, infection of hamsters with the papovavirus present in primary epitheliomas produced epitheliomas in good yield but was not reproducibly associated with lymphoma induction. These data confirm the observation that the HaPV is the causative agent of epitheliomas, but they suggest clearly that HaPV is not the agent responsible for lymphomagenesis.

Experimental transmission of macaque AIDS by means of inoculation of macaque lymphoma tissue.

Acquired immuno-deficiency syndrome (AIDS) of macaques, an animal model for human AIDS, was transmitted to previously healthy macaque monkeys by means of inoculation of either tissue or a cell-free filtrate of a macaque lymphoma. The recipients showed evidence of profound lymphocyte dysfunction or died with infections from such opportunistic agents as Candida albicans, Cryptosporidium, and cytomegalovirus.

Transmission of naturally occurring lymphoma in macaque monkeys.

Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and cryptosporidiosis. They also showed evidence of an abnormal circulating peripheral blood mononuclear cell. These findings, all characteristic of the acquired immune deficiency syndrome (AIDS) of macaques, suggest a link between these transmissible lymphomas and AIDS in macaque monkeys.

B-cell and T-cell lymphomas and other associated diseases induced by an infectious DNA viroid-like agent in hamsters (Mesocricetus auratus).

Five epidemics of diffuse, poorly differentiated lymphocytic, immunoblastic, and plasmacytoid lymphoma induced by an infectious, horizontally transmitting viroidlike agent have occurred in two hamster facilities. Incidence summaries and pathologic characteristics of the lymphomas induced in LSH and LVG hamsters are presented. An elevated leukocyte count with a marked increase in neutrophils and a significant decrease in small mononuclear lymphocytes was detected in 5-week-old but not in 10- or 25-week-old LVG hamsters born in the facility contaminated with the lymphoma-inducing agent. Three-week-old LVG hamsters exposed to the contaminated facility showed no similar hematologic change at 5 weeks of age or 5 weeks of exposure. Several associated syndromes, including an intussusception disease, pyelonephritis, inflammatory bowel disease, and body warts associated with the presence of the causative viroidlike agent in the contaminated colonies are described. Details of the epidemiology of the disease, karyology, viral studies, and correlation with several epidemics in other laboratories are presented.

[Probability models of the spread of leukemias and lymphomas]. / Veroiatnostnye modeli rasprostraneniia leikozov i limfom.

Probability models of horizontal dissemination of leukemia and lymphoma are considered. An analysis of the statistics on human and cattle morbidity in the Latvian SSR failed to establish any correlation between relevant indices for humans and cattle. Nor did it point to any evidence in support of the hypothesis on horizontal dissemination of hemablastosis in cattle under natural conditions.

Unusual filterable oncogenic agent isolated from horizontally transmitted Syrian hamster lymphomas.

An outbreak of horizontally transmitted malignant lymphoma in an experimental hamster holding facility was previously reported. Retroviridae (oncornavirus) or other conventional oncogenic viruses (oncodnaviruses) could not be detected in these lymphomas by immunological methods, direct isolation procedures or electron microscopy but an infectious agents was clearly involved. The incidence of lymphomas during five recurrent epidemics ranged from 50 to 90% in young, inbred and random-bred Syrian golden hamster exposed. The agent seemed to be resistant to UV inactivation, formaldehyde vapour and other viricidal agents (chlorine and iodine), and stable for long periods in the absence of hamster hosts in the contaminated facility. Associated disease syndromes in exposed hamster included severe enteritis, pyelonephritis, the occasional appearance of warts, poor breeding efficiency and intussusception. We now report the successful, cell-free isolation of an unusual, filterable agent prepared in protamine sulphate buffer from primary and animal-passaged lymphomas, which produces lymphomas with good efficiency when injected subcutaneously (s.c.) into newborn Syrian inbred (LSH) and random-bred (LVG) hamster. The agent could be reisolated from these induced lymphomas and injected into other hamsters to reproduce the neoplastic condition. It showed characteristics suggested for a mammalian viroid (a non-encapsidated, DNase-sensitive low-molecular-weight, disease-causing, self-replicating, naturally infectious nucleic acid).

Naturally occurring leukemia viruses in H-2 congenic C57BL mice. I. High lymphoma incidence following milk-borne transmission of virus.

Two modes of transmission of ecotropic type C viruses occur naturally in C57BL mice: maternal (i.e., through milk) and genetic. By selection of virus-positive and virus-negative B10.ASgSn [B10.A (H-2a)] mothers and foster-nursing of C57BL/10ScSn [B10 (H-2b)] newborns, four sublines of C57BL mice were obtained: B10.A V+, B10.A V-, B10 V+, and B10 V-. (V+ denotes positive for milk-transmitted B-tropic virus; V- denotes negative for milk-transmitted B-tropic virus). Milk transmission of naturally prevalent B-tropic virus (V+ sublines) led to persistent infection of all offspring over at least 8 generations. Milk transmission of virus was associated with a very high incidence of lymphomas. The H-2 complex influenced the titers of virus after milk transmission, which were higher in B10.A V+ mice than in B10 V+ mice. H-2 control of virus titers, as measured by serum p30 assay, was confirmed in (B10.A V+ X B10 V+)F2 mice. Resistance to the virus was dominant, because serum p30 levels in F1 and H-2a/b F2 animals were similar to those in the B10 V+ subline and lower than those in the B10.A V+ subline. The H-2 complex also influenced the incidence of lymphomas (78 and 42%, respectively, in the B10.A V+ and B10 V+ sublines). Most B10.A V+ lymphomas were of T-cell origin, whereas most B10 V+ lymphomas were classified as non-T/non-B cells. Genetic transmission of virus (V- sublines) led to heterogeneous expression of both N- and B-tropic viruses, which thereby established the mottled trait for expression of genetically transmitted type C viruses in C57BL mice. Genetic transmission was associated with a low incidence of lymphomas that occurred in senescence.

Contacts among patients with hematological malignancies.

A survey was carried out in 2 country areas of New South Wales with the aim of defining contacts among patients with lymphoma, leukemia and myeloma, and of determining whether these were more numerous than among matched controls from the same localities. Cases were identified from records of the N.S.W. Central Cancer Registry and of local doctors and hospitals. 184 cases were found, corresponding to the expected number, and 145 patients, as well as the same number of controls, were interviewed. Of the 290 patients and controls surveyed 111 (38.3%) had had one or more contacts with other patients or controls (37.9% of patients and 38.6% of controls). There were 24 case-case pairs involving contacts among 33 individual patients, 23 control-control pairs involving 36 individuals, and 38 case-control pairs involving 66 individuals. A statistical analysis using a weighting system showed that numbers, closeness and duration of contacts among patients and patients did not differ significantly from those expected. These results thus provide no evidence in favor of the hypothesis that the diseases were transmitted from patient to patient in the survey areas.

Characterization of immune responses to spontaneous hamster lymphomas.

Tumor resistance could be induced against the transplantation of cell lines derived from spontaneous lymphomas that occurred in the third of three lymphoma epizootics in a hamster colony. Immunization of normal hamsters with irradiated lymphoma cells promoted resistance to homologous lymphoma challenge and prevented the development of spontaneous lymphomas when immunized hamsters were exposed to the contaminated colony. This immunity could be transferred in an adoptive transfer assay. Resistance to direct challenge was not extended to simian virus 40(SV40)-induced sarcomas carrying SV40 tumor-specific transplantation antigen nor to herpesvirus-induced carcinoma cells, indicating specificity. The nature of the antigen(s) involved was discussed.

Studies on the etiology of lymphomas in turkeys: isolation of reticuloendotheliosis in virus.

Studies of tissues from 25 normal turkey flocks and of 15 selected turkey lymphoid tumors revealed no Marek's disease or lymphoid leukosis viruses, although reticuloendotheliosis viruses (REV) were isolated from 3 flocks (2 with a history of neoplastic disease). The REV isolates were culturally and antigenically similar to the prototype REV strain T but were of low pathogenicity. Attempts failed to transmit 6 lymphoid tumors of diverse origin by inoculation into 2 strains of recipient turkeys. These data support an etiological role for REV in some though not all forms of turkey neoplastic disease.