Lymphotoxin: An anticarcinogenic lymphokine as measured by inhibition of chemical carcinogen or ultraviolet‐irradiation‐induced transformation of syrian hamster cells

Abstract

Syrian-hamster-derived lymphotoxin inhibits benzo(a)pyrene and ultraviolet carcinogen-induced in vitro morphologic transformation of diploid secondary passage hamster embryo cells. When lymphotoxin is added up to 4 days post carcinogen, the reduction in the frequency of morphologic transformation 6 days after carcinogen treatment varies directly with lymphotoxin concentration. The frequency of transformation does not change following re-feeding with lymphotoxin-free medium and incubation for 6 additional days. Furthermore, transformation by ultraviolet is prevented when cells are pulsed with lymphotoxin for as few as 6 hours after irradiation. Thus, lymphotoxin has the potential to irreversibly inhibit the first recognizable morphologic step of carcinogenesis.

Role of lymphotoxin in expression of interleukin 6 in human fibroblasts. Stimulation and regulation.

“…Lymphotoxin is a glycoprotein produced by activated lymphocytes (7,8,(25)(26)(27); it can inhibit the growth of a variety of cells transformed by chemicals or viruses (28,29). Many of the actions of lymphotoxin are similar or identical to those observed with TNF-a.…”

Lymphotoxin ? An immunologic hormone with anticarcinogenic and antitumor activity

“…Human lymphokine preparations can also be produced with high levels of lymphotoxin and no or minimal levels of interferon, and conversely preparations can be obtained with high levels of interferon and little lymphotoxin activity [47]. Thus, lymphokine preparations can be produced with high levels of lymphotoxin and little or no interferon in which the cytotoxic activities correlate directly with the lymphotoxin concentration [7][8][9]47].…”

“…Thymosin fractions (by definition) and tumor necrosis factor are not produced by the cells used to induce lymphotoxin. Guinea pig and Syrian hamster lymphokines can be produced with no detectable interferon activity [8,47]. Hamster lymphokine preparations induced by phytohemagglutinin, fetal bovine serum, concanavalin A, or antigenic stimulation with keyhole limpet hemocyanin of peritoneal or spleen leukocytes contain no interferon activity, with the lymphotoxin units in the preparations varying over more than a 50-fold range (Table 2).…”

“…Recently we have begun to appreciate that in many syngeneic situations there is a preferential cytotoxicity of lymphotoxin for tumor cells in contrast to nonmalignant cells, including the ability of lymphotoxin to alter the carcinogenic process [9,10]. While the growth-inhibitory and anticarcinogenic activities ascribed to lymphotoxin were initially observed with predominantly nonfractionated, dialyzed, or diafiltered lymphokine preparations [8,10,34,52], the activities are continually being confirmed in investigations in which more highly purified lymphotoxins are used [4,9,63]. Lymphotoxin can be produced by mitogen or antigen stimulation of leukocytes for periods ranging from 4 -8 h [23,46] to 5 -7 days [22].…”

“…Lymphotoxin, one of the lymphokines or immunologic hormones secreted by activated leukocytes, is cytotoxic for a variety of tumor cells [41,51,62] and is able to prevent the carcinogenesis process [8]. The term 'lymphotoxin' was created by Granger in 1968 [16] to denote the soluble product(s) of antigen-or mitogen-stimulated lymphocytes, or more properly leukocytes, since macrophages may be involved in its production [64], that cause cytolytic changes in nonleukocyte cells growing in the same culture.…”