Antigenic changes of a murine lymphoma by in vivo treatment with triazene derivatives

Fioretti, Maria Cristina; Nardelli, Bernardetta; Bianchi, Roberta; Nisi, C.; Sava, Gianni

doi:10.1007/bf00198973

Cited by 13 publications

(5 citation statements)

References 7 publications

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“…In this paper we report on the metastatic properties of BL6 cells treated with the mutagenic compound potassium p-(3-methyl-l-triazeno)benzoate (MM-COOK), a xenogenizing chemical of the triazene class [6,16,17] for which no D NA hypomethylating activity can be demonstrated, and show that decreased metastatic ability may I" To whom correspondence should be addressed. be an early indication of the immunogenic changes associated with xenogenization by this type of compound.…”

Section: Introductionmentioning

confidence: 99%

Changes in the tumorigenic and metastatic properties of murine melanoma cells treated with a triazene derivative

et al. 1989

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Treatment of B16/BL6 murine melanoma cells in vitro with the 'xenogenizing' agent potassium p-(3-methyl-1-triazeno)benzoate (MM-COOK) had a profound impact on the tumorigenic and metastatic properties of the tumor, an effect that was only detectable in immunologically intact hosts. The treated tumor cells gave rise to a considerably smaller number of experimental and spontaneous pulmonary metastases and displayed an impaired growth rate in vivo, but were highly tumorigenic and metastatic in irradiated recipients. Moreover, the drug-treated cells retained the in vitro growth pattern and plating efficiency of the parent line, and were able actively to immunize intact hosts. Studies aimed at clarifying the mechanisms responsible for the decreased metastatic potential of the cells treated with MM-COOK indicated the involvement of host immune responses largely mediated by cells in the T-dependent compartment with no major contribution of natural immunity effector mechanisms.

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Section: Introductionmentioning

confidence: 99%

Changes in the tumorigenic and metastatic properties of murine melanoma cells treated with a triazene derivative

et al. 1989

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“…The term chemical xenogenization indicates the production of stable cell variants with increased immunogenicity by exposure of tumor cells to chemicals acting as mutagens and/or gene activators [7,24]. The highly immunogenic sublines which result from mutagenesis of murine lymphomas with triazene derivatives [13,14] express new individual antigens, recognized by syngeneic cytotoxic T cells (CTL), that have been termed drug-mediated tumor antigens (DMTA) [6]. These antigens account for the decreased transplantability of the tumor variants resulting from xenogenization, and have been extensively characterized in in vivo and in vitro studies of cell-mediated immunity [19,25].…”

Section: Introductionmentioning

confidence: 99%

Cell-mediated immunity to chemically xenogenized tumors I. Inhibition by specific antisera and H-2 association of the novel antigens

Romani

Grohmann

Fazioli

et al. 1988

Cancer Immunol Immunother

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T cell-mediated proliferative and cytotoxic responses occur in vitro to syngeneic tumor cells antigenically altered by mutagen treatment. One such xenogenized variant of the murine L5178Y lymphoma elicits IgG antibodies reactive with determinants on variant cells that are not expressed at detectable levels on parental or normal cells of the same H-2d haplotype and are also unrelated to public specificities of H-2b or H-2k histocompatibility antigens. In the present study we investigated the effect of those antibodies on development of cell-mediated responses in vitro to the xenogenized cells used for induction of the humoral response. The proliferative reaction, generation of cytolytic activity and target cell lysis were all inhibited by the anti-xenogenized tumor immune serum, whereas the corresponding reactions to the parental cells by syngeneic or allogeneic effector lymphocytes were not. In order to investigate the possible H-2 association of T cell-mediated responses to xenogenized cells, we also examined the effect on those reactions of antibodies specific for Class I or Class II products of the H-2d complex. The results obtained suggested a role for I-Ad molecules in the T cell proliferative response to the xenogenized cells, and also indicated a preferential association of the cytotoxic response with H-2Kd determinants.

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“…laboratory have shown that treatment of murine lymphomas with triazene derivatives leads to alterations in immunogenicity, a phenomenon referred to as chemical xenogenization (Bonmassar et al, 1970;Fioretti, 1975;Fioretti et al, 1981), by analogy with the term first introduced by Kobayashi et al (1969). Each of the chemically xenogenized tumors is known to carry a distinctive set of drug-mediated tumor antigens (DMTA, Bonmassar et al, 1979), not detectable in the parental line, which make the xenogenized tumor antigenically foreign to the host of origin, thus causing the latter to resist challenge with high inocula of the drug-altered lymphoma (Bonmassar et al, 1972).…”

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confidence: 99%

Humoral response against murine lymphoma cells xenogenized by drug treatment in vivo

Romani

Mage

Puccetti

et al. 1985

Intl Journal of Cancer

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Treatment of murine lymphomas with triazene derivatives may lead to the appearance of novel drug-mediated tumor antigens, a phenomenon known as chemical xenogenization. Such antigens, which are capable of eliciting specific transplantation resistance in histocompatible mice, have been previously detected by in vivo and in vitro cell-mediated immune responses. In the present report we address the question of the humoral antibody response to a chemically xenogenized lymphoma. Histocompatible mice were given several injections of live cells of the xenogenized tumor. Ten days after each immunization, pooled sera from different animals were analyzed for Ab content by means of flow microfluorometry analysis and CEL-ISA assay. The results reveal that antibodies of both IgG and IgM classes capable of binding the xenogenized tumor can already be detected after one single sensitization. However, the Ab titer gradually increases through subsequent immunizations, reaching a peak level after 3-4 injections at a time when most of the humoral response is made up of antibodies of IgG class. The specificity of the anti-xenogenized tumor hyperimmune sera was subsequently investigated by its reaction with the parental, non-xenogenized line and with normal tissue cells of the same or allogeneic haplotypes. The data obtained point out that cross-reactivity with the parental line could be completely removed by absorption of the hyperimmune sera on parental cells, which removed most of the IgM antibodies. Moreover, the presence of an excess of anti-parental antibodies on the xenogenized tumor cells does not prevent the subsequent binding of the hyperimmune absorbed serum, thus indicating that the novel determinant(s) recognized on xenogenized cells are not spatially related to those shared with the original parental tumor. In addition, the hyperimmune absorbed serum does not cross-react with normal hemopoietic or lymphoid cells of the same (H-2d) or allogeneic H-2b and H-2k haplotypes. Furthermore, no alien histocompatibility antigens of H-2b or H-2k haplotypes could be detected on the xenogenized tumor cell surface. Taken together, these data provide evidence that chemical xenogenization of a murine lymphoma leads to the appearance of novel determinant(s) detectable by specific antibodies.

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Antigenic changes of a murine lymphoma by in vivo treatment with triazene derivatives

Cited by 13 publications

References 7 publications

Changes in the tumorigenic and metastatic properties of murine melanoma cells treated with a triazene derivative

Changes in the tumorigenic and metastatic properties of murine melanoma cells treated with a triazene derivative

Cell-mediated immunity to chemically xenogenized tumors I. Inhibition by specific antisera and H-2 association of the novel antigens

Humoral response against murine lymphoma cells xenogenized by drug treatment in vivo

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