Tumors In Syrian Hamsters Research Articles

Secretion of type E prostaglandins (PGE) by Syrian hamster tumor cells during contact in vitro with natural killer cells

Secretion of type E prostaglandins (PGE) by Syrian hamster tumor cells during contact in vitro with natural killer cells

Insertion of adenovirus type 12 DNA in the vicinity of an intracisternal A particle genome in Syrian hamster tumor cells.

In the adenovirus type 12 (Ad12)-induced hamster tumor T1111(2) about 10 Ad12 genome equivalents were integrated at different sites. One of the integrated copies proved unstable and was lost from the cellular genome or rearranged upon passage of the cell line, H1111(2), established from this tumor. This unstable site of junction between the left terminus of Ad12 DNA and hamster DNA and the preinsertion site from BHK21 hamster cells was cloned, sequenced, and analyzed. The junction site showed several peculiarities. At the left terminus of Ad12 DNA, the first 64 nucleotides were deleted. At a distance of 127 nucleotides to the left from this junction site, an internal dispersed fragment of Ad12 DNA comprising nucleotides 1290 to 1361 of the authentic Ad12 DNA sequence was inserted into cellular DNA in an inverted orientation relative to the complete Ad12 genome that was located in its vicinity. The 127-nucleotide sequence between the intact Ad12 genome and the separate 72-base-pair (bp) Ad12 DNA fragment was cellular, but it was not identical to the preinsertion sequence at this location. The sequences flanking the termini of the dispersed 72-bp Ad12 DNA fragment were characterized by direct repeats of 9 or 10 nucleotides. To the left of Ad12 nucleotide 1361 in the separate 72-bp fragment, about 620 cellular nucleotides followed which were identical at the occupied and at the preinsertion sites. It was conceivable that the separate 72-bp Ad12 DNA fragment and the cellular sequence of 127 bp to its right had been transposed en bloc from another unknown location. Abutting the 620 nucleotides of cellular DNA to the left of this block, the 3'-terminal sequence of an endogenous, intracisternal A particle (IAP) genome of hamster cells was detected. The possible significance of the proximity of an IAP sequence to an inserted Ad12 genome with respect to the transformation event, to the instability at this site, or to the transcriptional activity of this region is not known. The 620 bp of cellular DNA between the 72-bp Ad12 DNA fragment and the end of the long terminal repeat of the hamster IAP sequence was apparently of a unique type. Transcriptional activity was not found in the approximate region between nucleotides -620 (to the left) and +350 (to the right) relative to the site of Ad12 DNA insertion, but was found outside these boundaries.

Development of lung tumors in Syrian hamsters after mixed infection withMycoplasma pneumoniae and influenza virus

Development of lung tumors in Syrian hamsters after mixed infection withMycoplasma pneumoniae and influenza virus

Characterization of exogenous proviral sequences in hamster tumor cell lines transformed by Rous sarcoma virus rescued from XC cells

Alterations in viral structural genes have been studied in five cell lines derived from Syrian hamster tumors which had been induced by the virus rescued from XC cells by transfection. Two cell lines, H-18 and H-20, have all the viral structural genes expressed, but a new EcoRI recognition site appeared in the region of the pol gene sequence. Provirus present in H-12 lacks the 3′ part of the gag gene sequences as well as the pol gene, therefore, it gives rise to an anomalous 1.8 Md EcoRI fragment. This line also does not synthesize viral RNA of genomic size, and none of the subgenomic RNAs found hybridized with the DNA itpol probe. The H-19 cell line harbors only the src gene and LTR sequences, the U 3 part of which seems incomplete or different from that of PR-RSV. The cryptic proviral structure in H-19 is transcribed into src mRNA. The degree of transcription of the src gene is about 25 viral RNA equivalents per cell. The H-9 cells harbor the complete provirus and, in addition, proviral structures having the deletion in gag-pol genes. The possible ways of development of provirus alterations and the role of cryptic proviral sequences in oncogenesis are discussed.

Induction of respiratory tract tumors in Syrian golden hamsters by a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the effect of smoke inhalation.

Four groups of 10 male and 10 female Syrian golden hamsters were given single s.c. injections of either 0.3 ml of trioctanoin or of 0.3 ml of trioctanoin containing either 1.0 mg, 3.3 mg, or 10.0 mg of the tobacco specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These hamsters were then exposed to cigarette smoke for the next 72 weeks. Four control groups received the same injections of NNK or trioctanoin but were treated by sham smoking. All groups treated with NNK had tumors of either the lung, nasal mucosa, and/or trachea. These tumors were not observed in hamsters injected with trioctanoin. These results demonstrate that even a single dose of NNK can induce respiratory tract tumors in Syrian golden hamsters. Smoke inhalation did not result in an increase in respiratory tract tumor incidence in most of the NNK treated groups.

Behavior of primary and serially transplanted estrogen-dependent renal carcinoma cells in monolayer and in collagen gel culture.

When estrogen is present in culture medium, enzyme-dissociated cells from estrogen-induced primary renal tumors in Syrian hamsters and from 1st to 4th serially transplanted carcinomas in monolayer culture contain progesterone receptor levels that are similar and comparable to those in tumors in vivo (i.e., 2 pmol/3×106 cells). Despite the similarity of receptor levels in cultured cells isolated from primary and transplanted tumors, the ability of cells to be maintained in culture differs considerably from one tumor stage to another. When cultured as monolayers in plastic flasks, isolated cells from primary tumors exhibit a marked decline in cell number after 4 to 6 d in culture. On the other hand, monolayer-cultured cells from first and second transplantation tumors remain essentially constant in cell number over a 2 wk culture period and cells from third transplantation tumors undergo a two- to threefold increase in cell number during 2 wk in culture. When primary tumor cells are cultured in collagen gels, the decline in cell number over a 2 wk culture period is prevented and progesterone receptor levels remain elevated. Cells cultured from first transplantation tumors exhibit a delayed decline in cell number beginning after 2 wk in monolayer culture. The decline in cell number in monolayer culture, like that for cells from primary tumors, can be prevented by culturing cells from first transplantation tumors in collagen gels. Neither cells from primary nor first transplantation tumors exhibit significant increases in cell number in collagen gels. Increasing the serum concentration of growth medium to 30% does not stimulate growth of cells under these conditions. Cells isolated from fourth transplantation tumors undergo a fourfold increase in cell number over a 1 month culture period whether cells are cultured as monolayers or in collagen gels.

The carcinogenicity of N-nitrosodiethanolamine, an environmental pollutant, in Syrian hamsters

Weekly subcutaneous injections of N-nitrosodiethanolamine (NDELA) at doses of 1000, 500 and 250 mg/kg body wt for life induced tumors in Syrian hamsters which primarily affected the upper respiratory tract. The incidence of these malignant neoplasms arising exclusively from the olfactory region was between 73% (highest dose) and 35% (lowest dose). Lower numbers of neoplasms were found with decreasing frequency in the trachea, larynx and lungs. The results indicate that doses of NDELA lower than 250 mg/kg body wt may also be carcinogenic. Hence, NDELA and its precursors should be regarded as hazardous to human health.

Modifications of the lymphoid B and T cell populations in spleen and thymus of tumor-bearing hamsters.

The golden Syrian hamster has proved to be a useful host for studying cell-oncogenic virus interaction, as many viruses induce neoplasms in this species. The first polyoma-induced tumors in Syrian hamsters were described in 1958 (1). Shortly thereafter, other authors (2) also noted that hamster cells could be transformed by this agent in vitro. After the discovery of the tumor-inducing potency of the polyoma virus, simian vacuolating virus or SV40 also was shown (3,4) to induce tumors when injected into newborn hamsters and to transform hamster fibroblasts in vitro.

A relationship between SV40-transformed cell susceptibility to macrophage killing and tumor induction in rodents.

Simian virus 40 (SV40) is a papovavirus that induces tumors in golden Syrian hamsters and transforms cells from many species in tissue culture (1). The ability of SV40-transformed hamster cells, but not cells from other species transformed by SV40, to induce tumors in the host (2) implies that in transformation of hamster cells, SV40 may induce a species-specific change that renders the neoplastic cells resistant to rejection by the host. Previous studies by the authors suggested that LSH hamster cells transformed by adenovirus 2 (Ad2, a human virus not oncogenic in newborn hamsters) (3,4) are susceptible to rejection by a thymus-dependent, cell-mediated host response (5,6,7). The resistance of SV40-transformed LSH cells to rejection by syngeneic animals and the recent observation that SV40-transformed LSH cells induce tumors in histoincompatible CB hamsters almost as efficiently as in syngeneic animals (8) support the hypothesis that SV40 alters the efficiency with which the hamster cells it transforms are recognized or destroyed by the host.KeywordsTarget CellGolden Syrian HamsterPeritoneal Exudate CellTumoricidal EffectHamster Cell LineThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Induction of benign and malignant lip tumors in Syrian hamsters by topical application of N-nitrosobis(2-oxopropyl)amine and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine

Weekly topical application of equitoxic doses of N-nitrosobis(2-oxopropyl)amine (BOP) or N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) to lip and/or vagina of female Syrian hamsters led to the development of papillomas and carcinomas of the lip, papillomas of the vagina, and tumors of internal organs. The relative incidence of the tumor types is affected by the dose of BOP or HPOP administered. BOP is excreted unchanged and as HPOP in the saliva of Syrian hamsters injected subcutaneously with BOP and pilocarpin. This result may help to explain preliminary observations that subcutaneously injected BOP and pilocarpin also lead to lip tumors.

Association of Tumor Induction by Ultraviolet Light-Inactivated Adenovirus 2-Simian Virus 40 Recombinants With a Specific Segment of Simian Virus 40 DNA

The nondefective (ND) adenovirus 2 (Ad2)-simian virus 40 (SV40) hybrid Ad2+ND4, which contains the segment of the SV40 genome between map positions 0.11 and 0.59, induced tumors in Syrian golden hamsters after inactivation by UV light. Ad2 and the Ad2+ND2 hybrid, which contains the segment of the SV40 genome between map positions 0.11 and 0.43, were not oncogenic after inactivation by UV light. These results showed that the incorporation of a specific segment of SV40 DNA into the Ad2 genome can alter the pathogenesis of the Ad2+ND4 virus by rendering it oncogenic for hamsters.

Growth of syngeneic transplantable tumors in Syrian hamsters immunized with embryonic hamster tissue

The effect of immunization with embryonic tissue on growth of two syngeneic transplantable tumors was investigated in Syrian hamsters. Immunization of inbred hamsters with embryonic hamster tissue followed by transplantation of continuous lines of syngeneic tumors was shown neither to inhibit nor to stimulate growth of the tumors. It is suggested that embryonic antigens do not participate in the mechanism of transplantation antitumor immunity.

Studies of estrogen induced renal tumours in male Syrian hamsters: 1. Cytochemical studies of lysosomal enzymes acid phosphatase and β-glucuronidase

The localization and concentration of lysosomal enzymes acid phosphatase and beta-glucuronidase in kidney cells of Syrian hamsters after DES administration were studied. A positive cytoplasmic reaction was demonstrated for both enzymes. Increased activity of these enzymes were observed in renal tumour in contrast to normal homologous cells. These results can be explained on the basis that lysosomal enzymes were synthesized in tumour cells at a higher rate or it may be due to the invasion of tumour tissue by hydrolase rich microphages.

Morphologic and histochemical characteristics of cell lines derived from hamster peripheral lung tumors

Intratracheal instillation of the alpha emitter polonium- 210 ( 210 Po) or benzo[a]pyrene induces peripheral lung tumors in Syrian hamsters which have a combined epidermoid and adenomatous morphology similar in appearance to human bronchiolar-alveolar carcinoma. Two permanent cell lines derived from such tumors have been studied in an attempt to determine the cell of origin of the original peripheral tumors. The ultrastructural and histochemical characteristics of both the cells and of cheek pouch tumors grown from HLAC- 4 and HLAC- 14 cells at various stages of passage in tissue culture in general support, but do not prove, our hypothesis that Clara cells found in the terminal and respiratory bronchioles are the cells of origin of the peripheral lung tumors induced in hamsters by these carcinogens.

Diallylnitrosamine: A Potent Respiratory Carcinogen in Syrian Golden Hamsters: Brief Communication2

Diallylnitrosamine (DAN), one of the few nitrosamines tested thus far that has not induced neoplasms in rats, caused a high incidence of respiratory tract tumors in Syrian golden hamsters treated sc with single or weekly doses of the compound. The effect was dose-dependent. The nasal cavity, larynx, and trachea were the most affected by DAN; most drug-induced tumors at those sites were adenocarcinomas and papillary polyps.

Role of Hormones in Growth Kinetics of Renal Cell Carcinoma in Vitro

Medroxyprogesterone acetate has been used to treat metastatic renal cell carcinoma largely because of its observed inhibitory effects on the growth of estrogen-induced tumors in male Syrian golden hamsters. The absence to date of any successful, established chemotherapeutic regimen in the management of metastatic renal cell carcinoma has led to the continued application of medroxyprogesterone acetate in the majority of patients with this disease because of the occasional regression witnessed (particularly in male patients) and the absence of untoward side effects. To examine the mechanism of action of medroxyprogesterone acetate renal cell carcinoma tumor cells from a patient who had responded to medroxyprogesterone acetate therapy were established in tissue culture. Cells were cultured in control medium, and in the presence of therapeutic and pharmacologic levels of medroxyprogesterone acetate. Tumor cell growth kinetics were determined by the incorporation of 3H thymidine. There was no growth inhibition effected by medroxyprogesterone acetate at therapeutic or pharmacologic levels. Therefore, the proposed salutary effect of medroxyprogesterone acetate in regression of metastatic renal cell carcinoma results from factors other than direct inhibition of renal cell carcinoma growth.

Experimental induction of melanotic tumors in syrian golden hamsters by transplacental and topical application of ethylnitrosourea.

Pregnant Syrian golden hamsters were treated with a single intra-peritoneal injection of ethylnitrosourea (ENU) solution a few hours pre-parturition. Offspring either received no further treatment or from 6 weeks of age, bi-weekly application of ENU solution in acetone for 20 consecutive weeks. Progeny from non, transplacentally treated mothers were also treated topically. Among all treated groups, 8.6% of the animals developed pigmented skin tumors, most of these animals having received the combined treatment. This group also showed a significantly decreased latency period in females compared to males. One of the skin tumors, which was histologically and clinically benign, was transplanted several times and subsequently exhibited malignant features.

Common metabolites of N-nitroso-2,6-dimethylmorpholine and N-nitroso-bis(2-oxopropyl)amine in the Syrian hamster

N-Nitroso-2,6-demethylmorpholine (NDMM) administered intraperitoneally to Syrian hamsters was metabolized to N-nitroso-bis(2-hydroxypropy)(2-oxopropyl)amine(HPOP) and N-nitroso-bis(2-hydroxpropyl)amine (BHP) which were identified in blood and urine. The potent pancreatic carcinogen N-nitroso-bis(2-oxoproply)amine was previously shown to form the same metabolites. Preliminary results indicate that NDMM also induces pancreatic and other tumors in Syrian hamsters, similar to those found following BHP treatment.

Induction of tumors in Syrian hamsters by a human renal papovavirus, RF strain.

Injection of RF virus (RFV), a papovavirus isolated from human urine, into newborn Syrian hamsters induced subcutaneous sarcomas in 50% of the recipients with 18- to 48-week latent periods. Transplantation of 2 X 10(6) primary RFV-induced tumor cells into weaning hamsters caused tumors in 100% of the recipients within 1-2 weeks. Continuous tissue culture cell lines were established from two primary tumors; one of these was transplantable. An in vitro-transformed continuous cell line (RF-194) obtained by infection of primary hamster embryo fibroblasts with RFV was transplantable in weaning hamsters. Neither infectious RFV nor virion antigens were detected in transformed cells. No RFV was recovered when transformed cells were fused with permissive, human embryo kidney cells by means of inactivated Sendai virus. Immunoperoxidase staining was used to show that all three RFV-transformed cell lines contained an intranuclear T-antigen closely similar to that of simian virus 40(SV40)-infected cells. Most hamsters (84%) with primary or transplanted RFV tumors responded with antibodies that reacted with RFV T-antigen and the T-antigen of SV40-infected cells. Likewise, hamster antisera against SV40 T-antigen cross-reacted with RFV T-antigen. Adsorption of RFV T-antisera with an excess of lyophilized SV40-transformed cells removed all detectable activity against SV40 T-antigen but left significant activity against RFV T-antigen. The reciprocal adsorption produced an antiserum spedicic for SV40 T-antigen. Thus human and simian papovavirus T-antigens were related but immunologically separable.

Studies on tumor variability. V. In vivo and in vitro investigations on H10Z tumor lymph node metastasis.

In vivo and in vitro investigations of a Syrian hamster tumor metastasis in the lymph node (H10Zm) in comparison with the primary tumor (H10Z) are performed. It is shown that the metastasis differs from the primary tumor by the prevalence of M secondary cell type characterized by globulous appearance, decreased adhesion and the presence of two long submetacentric marker chromosomes. Since a cell type with such cytogenetical characters was also found in the primary tumor as well as in a non-metastasizing tumor variant, it is suggested that the role of the induction-selection phenomenon in the occurrence of H10Z tumor metastases, i.e., new inductor agents occurred in the tumor's environment, might produce the induction of certain repressed mutant genes in M secondary cell type, bringing about certain phenotypical alterations (e.g., the decrease of the mutual cell adhesion) which could favorize the migration and selection of this cell type.