Liver Tumours volume

Three of the compounds evaluated in this volume (di(2-ethylhexyl) phthalate, di(2-ethylhexyl) adipate and cinnamyl anthranilate) are carcinogenic to the liver in mice and/or rats, and have been proposed to act by a mechanism involving peroxisomal proliferation in hepatocytes in those species. The role of peroxisome proliferation in evaluating carcinogenicity in humans has been discussed (lARC, 1995b). When, for any chemical, the relationship between peroxisome proliferation and liver tumours in rats or mice has been established, this should be considered relevant information in the evaluation of the possible risks for cancer in humans, taking into account the following ... 

Liver. Male B6C3Fi mice, four weeks of age, received a single intraperitoneal injection of 80 mg/kg bw TV-nitrosodiethylamine (NDEA) in tricaprylin. Two weeks later, the mice were fed diets containing 0, 3000, 6000 or 12 000 ppm di(2-ethylhexyl) phthalate for up to six months. Groups of 10 mice were killed at two, four and six months after NDEA treatment. Few hepatocellular foci were seen at two, four or six months in mice treated with NDEA alone or di(2-ethylhexyl) phthalate alone, while numerous foci and neoplasms were seen in mice given di(2-ethylhexyl) phthalate after NDEA. No tumours were found at six months in mice receiving NDEA alone. By the end of the study, the number of foci per unit volume of liver was similar in mice at all doses of di(2-ethylhexyl) phthalate, but there was an increase in the volume of the foci (0, 1.4, 0.6, 9.4 mm for the control, 3000-, 6000- and 12 000-ppm groups, respectively) (Ward et al., 1983). 

In rat liver, 1,2-dimethylhydrazine had no consistent effect on the relative focal volume of y-glutamyltranspeptidase-positive preneoplastic foci (Denda et al., 1988). Locniskar et al. (1985) treated Brown-Norway and Fischer rats with 150 mg/kg bw 1,2-dimethylhydrazine by gavage five times over a three-week period. Five months after the final treatment, isolated splenic, colonic intraperithelial lymphocytes and lamina propria lymphocytes from the Brown-Norway strain exhibited low natural killer cell activity and reduced splenic T-lymphocyte proliferation in response to autologous non-T lymphocytes. Furthermore, colonic lamina propria lymphocyte proliferation was low, and Brown-Norway rats had a low incidence of 1,2-dimethylhydrazine-induced colonic neoplasms (7%) in comparison with Fischer rats, which had more effective splenic and colonic intraperithelial lymphocyte natural killer cell activity, enhanced splenic autologous mixed lymphocyte response, enhanced colonic lamina propria lymphocyte proliferation and a higher incidence of colon tumours (20%). 

In some patients with a large volume of tumour in the liver, not suitable for potentially curative surgery or treatment with radiofrequency, RF ablation is increasingly being requested by the oncologists to reduce tumour bulk in the hope that this will increase the effectiveness of chemotherapy. The effectiveness of RF for this purpose requires further investigation. 

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