Increased tissue histamine in tumour-bearing mice and rats

Abstract

Summary.-Tissue histamine levels were studied in C3H and C57BL/6 mice bearing a methylcholanthrene-induced fibrosarcoma, in Wag rats bearing an aflatoxin B, -induced hepatoma, and in Commentry rats bearing a grafted hepatoma. Histamine levels were significantly higher (1-5 to 3 fold) in the tumour-bearing animals for ventral and dorsal skin, skeletal muscle and stomach fundus. Total histamine content was increased in the spleen.In C3H mice with McC3-1 fibrosarcoma, the excision of the tumour or its partial regression by intratumoral injections of Corynebacterium parvum induced a reversion to normal values.The tumour thus appears responsible for the increased histamine levels in tissues distant from the tumour.IN AN EARLIER STUDY, Lynch & Salomon (1 977a) compared the intensity of immediate hypersensitivity (anaphylactic type) reactions in normal C3H mice to those in mice carrying a 3-methylcholanthrene-induced fibrosarcoma (McC3). The intensity of active or passive anaphylactic shock decreased in the tumour-bearing mice. This was also the case for passive cutaneous anaphylaxis, the inhibition being strongest when the tumour was large. These results led us to investigate whether modifications of tissue histamine content could account for the diminished immediate hypersensitivity in tumourbearing mice. We had previously shown that, in many tissues (skin, skeletal muscle, stomach, kidney and blood) of C3H fibrosarcoma bearing-mice, the histamine levels were significantly higher than in normal mice (Scheinmann et al., 1979).The aim of the present work was to discover whether this apparently paradoxical increase in histamine levels in tissues distant from the tumour 1) could be found in other animals bearing other tumours, and 2) was dependent on the presence of the tumour. MATERIAL AND METHODS Animals and tumoursWag rats bearing a hepatoma.-Male rats (Wag strain) were fed from the time of weaning on a diet containing 250 ,ug/kg aflatoxin B1. Such a diet induces hepatomas in all rats and a small percentage of kidney tumours. In the present study, the animals were killed at 16 months and all of them were hepatoma-bearing. Ten males of the same breeding were used as controls.Commentry rats bearing a grafted hepatoma.-The LF hepatoma was a 4-dimethylaminoazobenzene-induced transplantable hepatoma. It was inoculated i.p. into 20-day old male rats of the same strain. The animals were killed 7-16 days after transplantation. Ten males of the same breeding were used as controls.C57BL/6 mice carrying a grafted fibrosarcoma.-The McB6-1 tumour is a fibrosarcoma induced by s.c. injection of 2 mg of 3-

Pilot study?cimetidine enhances lymphocyte infiltration of human colorectal carcinoma

“…The authors had already reported that perioperative lymphocyte func-10 08 M, much higher levels can be found in interstitial fluid and particularly within solid malignancies. [26][27][28] tion was preserved in these colon carcinoma patients by cimetidine. 11 An initial review of the routine pathoThese tumor levels of histamine are certainly above those that the authors demonstrated to suppress lymlogic reports found that patients receiving cimetidine did in fact demonstrate a higher level of immunoreacphocyte function in vitro.…”

Tissue histamine levels in male and female normal and nude mice

“…Animals were always killed between 14.00 and 16.00 to avoid possible diurnal variation in tissue histamine levels. Freshly collected tissues were treated as previously described [6].…”

Effect of Cimetidine on Intratumoral Cytokine Expression in an Experimental Tumor

“…Histamine is also known to be a modulator of malignant tumor growth (5). For example, a high histamine content was detected in proliferative tissues and in tissues from tumor-bearing animals (6,7). High HDC activity (5, 7) and rapid histamine synthesis (8) have been demonstrated in some types of tumors.…”