An in vivo mouse model was developed in order to study the characteristics of secondary tumor induction by cytostatic drug combinations used in human anticancer treatment. In this model we have proved the carcino-leukemogenic effects of widely used chemotherapeutical drug combinations (CHOP, COPP, COPBLAM, VAM). The carcinogenic hazards of cyclophosphamide and other alkylating drugs could also be demonstrated in our model.

Animals↗

PubMedDate not supplied

Effect of different cytostatic protocols on oncogene expression in CBA/Ca mice.

In vivo investigations on oncogene action may provide new findings on the toxicology of potential carcinogens. In this study we investigated the early effects of different cytostatic protocols on early oncogene expression in CBA/Ca mice. Most of the examined protocols showed detectable early changes, especially those containing cyclophosphamide. The most frequently involved oncogenes were N-ras, c-myc, and c-myb.

Animals↗

PubMedDate not supplied

Establishment and characterization of an EBNA-negative human lymphoma cell line (BHL-89).

BACKGROUND: The aim of the work was to establish human malignant lymphomas in culture, in order to study the biological characteristics and drug sensitivity of lymphomas of human lymphoid origin. MATERIALS AND METHODS: Lymph nodes of patients were explanted and kept in cultures using conventional tissue culture methods. Cytogenetic methods were used for karyotype analysis. Clonogenic assay was applied to test drug sensitivity. The tumorigenic capacity of the cells was determined by inoculating them into immunosuppressed mice. Immunological and other markers were examined with conventional techniques. RESULTS: A cell line, BHL-89, was established in culture from a patient with B-cell type non-Hodgkin's malignant lymphoma. Cells started to grow after a few days without a feeder layer in stationary suspension. The population doubling time was 48 h. The cells were hyperploid, and non-random aberrations were +1, -15, +14q+. Cloning efficiency in soft agar was found to be as high as 50-60%. The cells expressed markers characteristic of early B cells. The BHL-89 cells were Epstein-Barr nuclear antigen (EBNA) negative. They produced tumors when 10(7) cells were injected into immunosuppressed mice. The cells were sensitive to dibromodulcitol (Elobromol), an alkylating antitumor drug, and resistant to the phorbol ester TPA. CONCLUSIONS: The established EBNA-negative BHL-89 cell line has a few unique characteristics, e.g. rapid establishment without feeder cells, origin from the lymph node of an adult patient, high clonogenicity in soft agar, and resistance to TPA. The cell line is suitable for studying the nature of B lymphomas and testing compounds against lymphoproliferative disorders.

Antigens, Viral↗

PubMedDate not supplied

In vivo effects of COPP protocol on onco- and suppressor gene expression in a 'follow up study'.

In vivo investigation of onco or suppressor genes may provide new information concerning chemical carcinogenesis. In earlier studies we illustrated the carcinogenic potential of COPP chemotherapeutical protocol in "long term" experiments. Elevated expression of oncogenes was shown as soon as 24 hours after treatment in CBA/Ca inbred mice, in "short term" experiments. Now we present the results of the follow-up study dealing with the carcinogenic effect of COPP. The genes most frequently involved were N-ras and p53, with the thymus being the target organ of COPP.

Animals↗

PubMedDate not supplied

Effect of ABVD therapeutic protocol on oncogene and tumor suppressor gene expression in CBA/Ca mice.

The in vivo investigation of onco/suppressor gene effects may provide new information on chemical-environmental carcinogenesis. We previously described the elevation of onco/suppressor gene expression due to CHOP and COPP chemotherapeutical protocols in a CBA/Ca mouse model. Below we describe the results of the onco/suppressor gene expression studies after treatment with ABVD, a non-cyclophosphamide containing protocol. Expression of c-myc, Ha-ras, and p53 genes was investigated 1/2, 1, 3, 6, 12, 24 hours, 2 6 30 days, 6, and 12 months after treatment with a single dose of ABVD protocol. RNA was isolated from the thymus, spleen, liver, bone marrow, kidneys, and hybridzed with chemiluminescently labelled probes of Ha-ras, c-myc, and p53 genes. Significant changes of gene expression was found in the spleen and thymus, even after 30 minutes. The female spleen seemed to be more sensitive than the male one, but no sex difference was observed in the thymus. No significant alteration was detected in the other investigated organs.

Animals↗

PubMedDate not supplied

In vivo effects of CHOP protocol on onco and suppressor gene expression: follow-up study.

In vivo investigation of onco/suppressor gene effects may provide new findings concerning chemical carcinogenesis. In earlier studies we pointed out the carcinogenic potential of COPP and ABVD chemotherapeutical protocols in "long-term" experiments. In another follow up study we proved the connection between the early gene expression changes and the late consequences of COPP and ABVD treatment during, a one year latency period. CHOP protocol is containing both proved carcinogenic cyclophosphamide and highly mutagenic doxorubicyn. CHOP protocol in "short-term" experiments shows strong effect on Ha-ras oncogene expression.

Animals↗