METABOLIC CARCINOGENESIS^|^mdash;INDUCTION OF MURINE LYMPHOMA BY CO2-TREATMENT IN VIVO AND IN VITRO

Abstract

SUMMARY: Metabolic carcinogenesis may be viewed as a process in which a chronic disturbance of metabolic homeostasis leads to malignancy . Fluctuation in the CO2 tension in tissues is accompanied by changes in the intracellular pH . This prompted investigations into the long-term clinical effects of high CO2 tensions on various normal tissues in mice by two different methods. The first consisted of exposing different tissues in vitro to a high C02% in air before transplantation into syngeneic or autologous hosts. The second method consisted of exposing intraperitoneal tissues in vivo to C02-infusion, thus avoiding graft-host interactions .This is a report of the most significant findings in the series of investigations analyzed, 1. High incidences of malignant lymphoma in strains of mice with a low or zero spontaneous incidence followed: (a) syngeneic transplantation , (b) autologous transplantation, (c) in vivo exposure to CO2-infusion.2. Syngeneic graft recipients developed similar high lymphoma incidences, irre spective of the tissue grafted or the pretransplantation treatment of the graft . 3. In the autologous system, however, the clinical results reflect the differences in the pretransplantation treatment, in contrast to those in the syngeneic system . 4. Whereas intraperitoneal CO2-infusion induced lymphoma , air-infusion did not. 5. Non-lymphoid grafts exposed in vitro to elevated CO2 induced only lymphoid malignancies. But non-lymphoid tissues exposed in vivo to elevated CO2 developed tumors of other tissues, such as lung tumor, in addition to lymphoid malignancies.6. The same morphological lymphoid abnormalities occurred in all lymphomadeveloping animals in these three experimental models. Hyperplasia in the splenic T-cell areas appeared most frequently.7. The presence of immune-associated lesions in experimental animals (amyloidosis, interstitial nephritis and myocarditis) points to the activation of immune mechanisms in this lymphoma development.

Toxicity of Carbon Dioxide: A Review

“…The long-term clinical effects of high CO 2 tensions on various normal tissues in mice have been investigated . Different tissues were exposed in vitro to a high CO 2 proportion in air (45% CO 2 ) before transplantation into syngeneic or autologous hosts, or, in a second protocol, intraperitoneal tissues were exposed in vivo to CO 2 -infusion (99.99%), thus avoiding graft–host interactions.…”