Liver tumour

In a typical tumour ECT, a direct current (d.c.) voltage of 8.5 V is applied between two platinum electrodes inserted 3 cm apart in a cancerous tissue (e.g., liver tumour), causing a flow of 30 mA electrolysis current this current is made to flow continuously for... 

Dydrogesterone is a progesterone analogue. One of its indications is endometriosis, in which case dydrogesterone is administered at a dose of 10 mg two to three times daily. Progestogens are contraindicated in severe liver impairment and in patients with a history of liver tumours. 

Because woodchuck hepatitis virus is similar to human hepatitis B, that rodent is a good animal model for the infection. McKenzie et al. followed the development in woodchucks of hepatocellular carcinoma arising from the infection over 6 months using P 2D MRSI. They attributed the increased ratio of PME/(3-NTP to increased cellular proliferation of the liver tumour. 

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 ... 

As part of a larger experiment for studying the characteristics of hepatocarcino-genesis, 17 male Fischer 344 rats were fed a diet containing 2% (20 000 ppm) di(2-ethylhexyl) phthalate [purity unspecified] for up to 78 weeks. A group of 18 untreated animals served as controls. At 52 weeks, no liver tumours had developed in 10 di(2-ethylhexyl) phthalate-treated rats or in 10 controls, while at 78 weeks, hepatocellular carcinomas or neoplastic nodules were found in 3/7 di(2-ethylhexyl) phthalate-treated rats and 0/8 controls (Hayashi et al., 1994). 

Similarly, modulation of hepatocellular proliferation by peroxisome proliferators has been implicated in the mechanism of carcinogenesis. This can theoretically result in increased levels of mutation by increasing the frequency of replicative DNA synthesis as well as increasing the number of hepatocytes at risk. Furthermore, hepatocellular proliferation is probably involved in the promotion of growth of pre-neoplastic hepatocytes. There is clear evidence that di(2-ethylhexyl) phthalate causes acute and sustained hepatocellular proliferation under bioassay conditions which resulted in liver tumours in rats (Marsman et al., 1988). 

The weight of evidence for di(2-ethylhexyl) phthalate and its metabolic products demonstrates that they do not act as direct DNA-damaging agents. Di(2-ethylhexyl) phthalate produces liver tumours in rats and mice. 

Overall, these findings indicate that the increased incidence of liver tumours in mice and rats treated with di(2-ethylhexyl) phthalate results ifom a mechanism that does not operate in humans. 

In making its overall evaluation of the carcinogenicity to humans of di(2-ethyl-hexyl) phthalate, the Working Group took into consideration that (a) di(2-ethylhexyl) phthalate produces liver tumours in rats and mice by a non-DNA-reactive mechanism involving peroxisome proliferation h) peroxisome proliferation and hepatocellular proliferation have been demonstrated under the conditions of the carcinogenicity studies of di(2-ethylhexyl) phthalate in rats and mice and (c) peroxisome proliferation has not been documented in human hepatocyte cultures exposed to di(2-ethylhexyl) phthalate nor in the liver of exposed non-human primates. Therefore, the mechanism by which di(2-ethylhexyl) phthalate increases the incidence of hepatocellular tumours in rats and mice is not relevant to humans. 

Di(2-ethylhexyl) adipate produces liver tumours in mice. 

Dietary levels administered to miee and rats in a eareinogenesis bioassay and assoeiated with inereased ineidenee of liver tumours in mice, but not in rats (National Toxieology Program, 1980). 

Table 7. Effect of various dichloromethane inhalation exposure regimens on survival and pulmonary and liver tumours in female B6C3Fi mice...

Carbon tetrachloride was tested for carcinogenicity in several experiments in mice by oral and intrarectal administration and in rats by oral and subcutaneous administration and by inhalation exposure it was also tested in one experiment in hamsters and one experiment in trout by oral administration. In various strains of mice, it produced liver tumours, including hepatocellular carcinomas. In various strains of rats, it produced benign and malignant liver tumours and in one experiment with subcutaneous injection, an increased incidence of mammary adenocarcinomas was observed. In hamsters and trout, increased incidences of liver tumours were observed however, these studies were considered to be inadequate (lARC 1979). 

Groups of 11-15 male Syrian hamsters, six weeks of age, were administered carbon tetrachloride by gavage at a dose of 0 or 0.1 mL/animal every two weeks for 30 weeks alone or beginning one week after a single intraperitoneal injection of 6 mg/kg bw NDEA. At the end of the study at 30 weeks, carbon tetrachloride alone produced no liver tumours compared with 1/15 (7%) in hamsters given NDEA and 11/13 (85%) in hamsters given NDEA followed by carbon tetrachloride (Tanaka et al., 1987). 

Although a few liver tumours were observed in male mice, these experiments were... 

Trichloroethane was tested for carcinogenicity by oral administration in rats in two experiments and in mice in one experiment. Although leukaemia was seen in both sexes of rats in one study and a few liver tumours occurred in male mice, the results of these studies were considered to be inadequate for evaluation. 1,1,1-Trichloroethane was tested by inhalation in rats in two experiments and in mice in one experiment. No chemically related increase in tumour incidence was observed in either rats or mice in one adequate study. Another inhalation study was considered to be inadequate. 

Hydrazine was tested for carcmogenicity by oral administration to mice in several experiments, producing mammary and lung tumours. When tested by oral administration or inhalation exposure in rats, it produced lung, liver and nasal tumours and a few colon tumours. In hamsters, it produced liver tumours and thyroid adenomas following oral or inhalation exposure. 

Rat. 2-Nitropropane (redistilled) was administered by gavage to weanling male Sprague-Dawley rats at a dose of 1 mmol/kg bw three times per week for 16 weeks. All surviving rats were killed at week 77. Benign liver tumours appeared in 4/22 treated animals versus 1/29 controls and malignant liver tumours occurred in 22/22 treated rats versus 0/29 controls (/ < 0.001) (Fiala et al.. 1987a). 

Nitropropane was tested for carcinogenicity in one experiment in rats by oral administration and two experiments in rats by inhalation exposure. It induced benign and malignant liver tumours following oral administration and hepatocellular carcinomas in one inhalation experiment and an increased incidence of hepatocellular nodules in the other. 2-Nitropropane showed initiating activity in rat liver in two experiments. 

Acetamide was tested for carcinogenicity by oral administration in rats, producing benign and malignant liver tumours (lARC, 1974). 

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