Biomedical subjects
Publications and source records attributed to A Fray.
Dimaprit, a histamine H2-receptor agonist, injected daily i.p. to fibrosarcoma-bearing mice, induced a decrease in tumour growth and an increase in survival. Dimaprit, added to tumour cell cultures (10(-4) M), inhibited the incorporation of 3H-thymidine while embryonic cell cultures were unaffected. This particular anti-tumour activity is probably H2-independent as histamine and impromidine have no effect on tumour cell cultures.
The influence of mast cells on tumor incidence and growth rate was studied in 2 grafted tumor models (fibrosarcoma MC-B6-1 and the Lewis lung carcinoma 3LL). Three kinds of WBB6F1 mice (a cross between WB/ReJ-W/+ and C57BL/6J-WV/+ mice) were used: W/WV (deeply mast cell depleted), WV/+ (partially mast cell depleted), and +/+ (normal mast cell number). The presumed resistance of F1 hybrids to tumor cells of parental origin was observed in 12 of 13 +/+ mice, but only in 11 of 22 WV/+ mice and in none of 39 W/WV mice. Tumor incidence and metastasis incidence were inversely correlated with tissue histamine levels and mast cell number. Growth rates of tumors were similar in W/WV and WV/+ mice, but the tumor growth rate was much slower in the only +/+ mouse in which the tumor grew. These results confirm the protective role of mast cells against tumors.
In C57BL/6 mice bearing the 3LL carcinoma and in C3H mice bearing the McC3 -1 fibrosarcoma (18th passage), the increase in skin histamine levels was correlated with the increase in mast cell number. The number of cells able to incorporate tritiated thymidine was proportional to the mast cell number. These results strengthen the notion that, in tumour-bearing rodents, the increase in tissue histamine is an active phenomenon.
Histamine levels increased in the fundus of mice bearing a primary 3-methylcholanthrene-induced fibrosarcoma, and in the ventral skin, skeletal muscle and rumen of rats bearing a D.M.B.A. induced mammary adenocarcinoma; they did not increase in the tissues of mice bearing a McC3-1 fibrosarcoma (38th passage) or a Lewis lung carcinoma before the appearance of metastasis, but an increase in histamine levels was observed in dorsal skin, ventral skin and fundus, after the appearance of metastasis.
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Lewis lung carcinoma(3LL) cells grafted in syngeneic adult C57BL/6 mice produced local tumours associated with lung metastasis in 78% of recipients. Adult thymectomized, lethally irradiated, bone marrow cell-reconstituted animals (B mice) were more resistant since this tumour grew in only 46% of recipients and especially the weight of lung metastasis was almost 8 times less than in normal animals. Sera from tumour-bearing mice transferred into B mice enhanced tumour incidence and weight of metastasis to the level observed in normal mice. In vitro cultured 3LL cells displayed an intense mitogenic activity as measured by 3H-thymidine incorporation. Addition into these cultures of serum from tumour-bearing animals did not alter this activity. Addition of normal spleen cells in a ratio 40/1 reduced this mitogenic activity to a half or a third. Spleen cells from tumour-bearing mice, either normal or serum-enhanced B mice, mixed in vitro with 3LL cells, produced a 4-fold increase of mitogenic activity of the latter. These results indicate that the lymphoid system may contribute to the growth and spreading of 3LL tumours.
The effect of the irritant chosen to provoke the peritoneal exudate in donors of cells for the in vitro migration inhibition test was studied. Guinea-pigs with delayed hypersensitivity to tubercle bacilli were used. Irritants studied included starch, Bayol and thioglycollate medium. The exudates obtained with thioglycollate were found to show greater inhibition than those obtained with the other irritants in the in vitro response to PPD, Inhibition of migration was seen when 1 microgram/ml of PPD was added to the culture medium; with this dose the inhibition of migration was 53%. The state of activation of macrophages caused by the irritant thus appears to have some importance for their responsiveness to factors liberated by specifically sensitized lymphocytes.
Cytotoxic and cytostatic properties of peritoneal exudate cells from BALB/c mice either normal or pretreated with Corynebacterium parvum normal were studied using as target cells two lines of BALB/c fibroblasts one normal (BALB) and one transformed by Kirsten virus (K.BALB).. C. parvum activated cells displayed higher cytotoxic as measured by 51Cr or 3H-thymidine release and cytostatic, as measured by 3H-thymidine incorporation, activities against these lines of syngeneic cells. Cytotoxic effect of normal peritoneal cells was evident when 51Cr or 3H-thymidine release was used whereas no such effect was found when cytolytic plaque formation test was used. Sensitivity of both BALB and K.BALB target cell lines was found to be equal to cytotoxic and cytostatic activities of C. parvum activated or normal syngeneic peritoneal cells.
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Adherent cells of peritoneal exudates were obtained from conventional, or from germ-free mice or from mice having received in intraperitoneal infection of a variety of phlogogenic substances such as Corynebacterium parvum (C. parvum) (Mérieux) 500 microgram, thioglycolate (Difco) 3 ml, Bayol (Esso) 0.50 ml + 0.50 ml culture medium, glycogene 1.2 ml. The cytotoxic properties adherent cells were studied in vitro by the chromium release technique (CRT) and their cytostatic properties by the inhibition of the incorporation of tritiated thymidine by YC8 lymphoma cells. C. parvum was found to be the most active agent in enhancing the cytotoxic properties of adherent cells, followed by BCG and Bayol. Glycogen peptone and other substrates were without effect. The unstimulated peritoneal macrophages of conventional mice were found to inhibit thymidine incorporation by tumour cells, whereas those of germ-free mice could not do so. C. parvum markedly increased the cytostatic property adhered cells from both germ-free and conventional mice.
The treatment by Corynebacterium parvum induced an increase of peritoneal cell number in conventional mice but no modifications in germ-free mice. Against YC8 tumoral target cells, cytostatic properties of peritoneal cells were of the same intensity in conventional and germ-free after C. parvum treatment. Against K.BALB cells, C. parvum treatment induced an increase of cytostatic properties from 9 to 93% in conventional mice and from 51 to 84% in germ-free mice. Cytotoxic properties were increased by C. parvum in conventional mice but were unchanged in germ-free mice. The bacterial flora could play a role in the cytotoxic and cytostatic properties of peritoneal cells in conventional mice.