Age-related and thymus-dependent rejection of adenovirus 2-transformed cell tumors in the Syrian hamster.

Adenovirus type 2-transformed hamster cell-induced newborn tumor lines were usually rejected when transplanted s.c. into 21-day-old syngeneic, weanling hamsters. The tumor-inducing capacity of two of these lines (Ad2HTL3 and Ad2HTL6) was tested in intact and neonatally thymectomized hosts. After s.c. injection of suspensions prepared from these lines, none of the weaning hamsters developed tumors while 100% of the newborns and 35.2% of neonatally thymectomized, weanling hamsters developed progressively enlarging neoplasms. The susceptibility of neonatally thymectomized hamsters to tumor challenge was directly related to the degree of immunosuppression observed following thymectomy as indicated by the amplitude of the in vitro response of blood leukocytes to concanavalin A. Pretreatment of thymectomized weanlings with syngeneic adult lymphoid cells (i.p.) resulted in a significant reduction in tumor susceptibility (p = 0.03). These findings suggest that acquisition of resistance to adenovirus type 2-transformed cells during the first 21 days of life may be a thymus-dependent cellular immune process.     

Lung tumors from PuO2-ZrO2 aerosol particles in Syrian hamsters

Syrian golden hamsters were given PuO2/ZrO2 particles via inhalation and/or Pu-laden ZrO2 ceramic 10-micron diameter microspheres lodged in the capillary bed of the lung. The mean initial lung burdens ranged from 8 nCi to 143 nCi for the six experimental groups of animals. Significant numbers of primary lung tumors (5-50% per group) were induced in those animals that received inhalation exposures. Additional alpha radiation administered via Pu-laden intravenous microspheres had little or no effect on tumorigenesis or the production of non-neoplastic, degenerative changes in the respiratory tract.     

Inhibition of streptozotocin-induced islet cell tumors and N-nitrosobis(2-oxopropyl)amine-induced pancreatic exocrine tumors in Syrian hamsters by exogenous insulin

The effects of streptozotocin (SZ) and N-nitrosobis(2-oxopropyl)amine (BOP), separately or in combination, on the pancreas, common duct, and gallbladder, all target tissues of BOP, were studied in Syrian golden hamsters. Groups of hamsters were treated with either a single dose (20 mg/kg body weight) of BOP (BOP group), or a single i.p. dose (50 mg/kg body weight) of SZ and 14 days later with a single s.c. injection of the same dose of BOP (SZ + BOP group). Another group of animals was treated similarly with BOP and SZ except that they received twice daily injections of insulin, beginning 1 day after SZ administration and for the duration of the experiment (52 weeks) (SZ + insulin + BOP group). The control group consisted of hamsters treated with a single dose of BOP and daily doses of insulin (insulin + BOP group). Hamsters treated with SZ recovered spontaneously from their diabetes, although the mortality was high (86%). BOP treatment inhibited the diabetogenic effects of SZ in both SZ + BOP and SZ + insulin + BOP groups and reduced the mortality to 43 and 74%, respectively. SZ pretreatment inhibited the incidence of BOP-induced pancreatic ductal/ductular cell carcinomas in the SZ + BOP group (P less than 0.01); this protective effect of SZ on carcinoma development was potentiated by additional treatment with insulin (SZ + insulin + BOP group, P less than 0.001). Although the frequency of BOP-induced tumors in the gallbladder (all polyps) was not altered by either SZ or insulin, the frequency of the common duct polyps was significantly lower in the SZ + insulin + BOP group than in the BOP group (P less than 0.005). Hamsters in the SZ, SZ + BOP, and SZ + insulin + BOP groups developed islet cell adenomas (insulomas). However, the SZ + insulin + BOP group had significantly fewer insulomas than in the SZ + BOP group (P less than 0.0005). The overall data confirm the inhibitory effect of SZ on BOP-induced pancreatic cancer and suggest that this effect is related to the diabetic condition of hamsters rather than insulin deficiency and that intact islets appear to be prerequisite for exocrine pancreatic cancer induction by BOP. On the other hand, the inhibitory action of insulin on insuloma induction by SZ and on ductal/ductular cancer induction by BOP seems to be related to the suppressive effect of this hormone on beta-cell and ductal/ductular cell replication, respectively.     

Virus-specific markers and virus-like particles in cell lines of tumors produced by CELO virus in Syrian golden hamsters.

Cell lines were established from 2 primary hepatocellular carcinomas (HC's) and 3 sarcomas produced in Syrian golden hamsters inoculated as newborns with chicken embryo lethal orphan (CELO) virus. Cell lines from 2 sarcomas (COT, CMT) and 1 HC (CEHEP) produced CELO virus-specific T-antigen. The antigen was not detected in cells of the third sarcoma line (RCT) until they had undergone more than 34 passages in vitro. Although 5-10% of cells in the second HC line (CILT/2) contained T-antigen during early passages, it was not demonstrable after the fifth subculture. Nevertheless, cells of both HC lines possessed CELO virus tumor-specific transplantation antigen. All 5 cell lines also contained hamster type R particles, and both HC lines had type C and intracytoplasmic type A particles. The percentage of carcinoma cells producing type R particles increased during cultivation in vitro, whereas the number of cells with type A particles decreased. Treatment with dibutyryl cyclic AMP and theophylline enhanced the number of cells producing type C particles in 1 HC line and type R particles in 2 sarcoma lines.     

Upper respiratory tract tumors induced in Syrian hamsters by N-methyl-N-nitrosourea

Syrian hamsters were treated weekly for 2 1/2 months by intratracheal instillation of N-nitroso-N-methylurea (NMU). All the animals, with the exception of one that survived to 11 months of age, were killed between 5 and 7 months because of severe respiratory insufficiency. Tumors, often multicentric in origin and frequently at different sites, developed in the nasopharyngeal tube, pharynx, larynx, trachea, bronchi, esophagus and forestomach. Histologically the tumors were epidermoid carcinomas. No distant metastases were observed. The results indicate that NMU exerts a strong local carcinogenic action when applied topically to the mucosa of the upper respiratory tract of Syrian hamsters. The wide spectrum of lesions, benign and malignant tumors, that occur following parenteral administration of NMU were not seen.     

Anti-HER-2 DNA vaccine protects Syrian hamsters against squamous cell carcinomas

This paper illustrates the efficacy of DNA vaccination through electroporation in the prevention of oral transplantable carcinoma in Syrian hamsters. At 21 and 7 days before tumour challenge, 19 hamsters were vaccinated with plasmids coding for the extracellular and transmembrane domains of rat HER-2 receptor (EC-TM plasmids), whereas 19 control hamsters were injected intramuscularly with the empty plasmid. Immediately following plasmid injection, hamsters of both groups received two square-wave 25 ms, 375 V cm(-1) electric pulses via two electrodes placed on the skin of the injection area. At day 0, all hamsters were challenged in the submucosa of the right cheek pouch with HER-2-positive HCPC I cells established in vitro from an 7,12-dimethylbenz[a]anthracene-induced oral carcinoma. This challenge gave rise to HER-2-positive buccal neoplastic lesions in 14 controls (73.37%), compared with only seven (36.8%, P<0.0027) vaccinated hamsters. In addition, the vaccinated hamsters displayed both a stronger proliferative and cytotoxic response than the controls and a significant anti-HER-2 antibody response. Most of the hamsters that rejected the challenge displayed the highest antibody titres. These findings suggest that DNA vaccination may have a future in the prevention of HER-2-positive human oral cancer.     

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.     

Carcinogenic effects of diethylstilbestrol in male Syrian golden hamsters and European hamsters.

The tumorigenic effects of sc-implanted diethylstilbestrol (DES) on male Syrian golden hamsters and European hamsters were compared. The adenohypophyses, kidneys, and testes of both species showed neoplastic responses to DES treatment. European hamsters were more sensitive than were Syrian hamsters, inasmuch as the European hamsters had a higher tumor incidence. The testicular tumors were all Leydig cell adenomas and seemed to depend on the coincident occurrence of hypophyseal neoplasms (all composed of gonadotropic cells). Of the European hamsters tested, 29% also developed liver tumors (hepatocellular adenomas, carcinomas, and cholangiocarcinomas.     

Carcinogenicity of 4-hydroxybutyl-butylnitrosamine in Syrian hamsters.

4-Hydroxybutyl-butylnitrosamine (HBBN), a urinary metabolite of dibutylnitrosamine (DBN) was shown to induce respiratory and bile duct tumors as well as carcinomas of the urinary bladder in Syrian golden hamsters. This contrasts with results previously obtained in rats and demonstrates that HBBN is not a specific bladder carcinogen. Bronchogenic tumors, seen in DBN-treated hamsters, were not observed after injection of HBBN.     

Blastomogenic activity of 2-aminoacetophenone in Syrian hamsters]

The blastomogenic activity of 2-aminoacetophenone (2-AAP)--one of the aromatic triptophan derivatives, found in the urine of leukemic patients, was studied on nonlineal Syrian hamsters, 2-AAP would induce the increased total incidence of tumors and raise the frequency of endocrine system tumors, especially adrenal adenomas. The results of the experiment indicate an insignificant blastomogenic activity of 2-AAP and correlate well with the results obtained on lineal mice.     

Characterization of drug metabolism enzymes in estrogen-induced kidney tumors in male Syrian hamsters

In an attempt to characterize metabolism enzymes of the estrogen-induced kidney tumor in male Syrian hamsters, the activities of enzymes involved in drug and glutathione metabolism were determined in tumor tissue. Kidney tumors were induced in male Syrian hamsters by treatment with estradiol for 8 months. Cytochrome P-450 and cytochrome b5 concentrations in tumors were below detectable levels. However, when cytochrome P-450-mediated oxidation was analyzed by product formation assays, the oxidation of E-diethylstilbestrol to diethylstilbestrol-4',4"-quinone by tumor microsomes was 10-20% of the rate found in control microsomes. In kidney tissue surrounding estrogen-induced tumors, cytochrome P-450 and b5 contents were 50-60% less than those in untreated kidney. Activities of reducing enzymes of drug metabolism (cytochrome P-450, cytochrome b5 and NADH:cytochrome c reductases), glutathione metabolism enzymes (glutathione peroxidase, glutathione transferase, glutathione reductase, and gamma-glutamyl transpeptidase), and free radical scavenging enzymes (superoxide dismutase, catalase, and quinone reductase) in tumor were significantly lower than in untreated kidney tissue. The activities of these enzymes in renal tumor surrounding tissue were between those observed in tumor and control kidney. Glucose-6-phosphate dehydrogenase activity was increased by 50% in surrounding tissue and 430% in tumor compared to values in untreated controls. The decreased enzyme activity levels in hormone-exposed tissue surrounding tumors likely represented an adaptation of this tissue to the neoplastic environment induced by chronic estrogen treatment.