Donald C. Williams

The effect of prolonged oral contraceptive steroid use on erythrocyte glutathione peroxidase activity.

A clinical study was undertaken to determine whether oral contraceptives (OCs) affect the activity of the enzyme glutathione peroxidase. OC users recruited for the study were volunteers attending the Redhill Family Planning Clinic in England. Their demographic characteristics were noted. Pre- and postmenopausal comparative subjects were also used. The laboratory procedures involved in the study are described. Findings are tabulated. The average erythrocyte glutathione peroxidase levels of women using OCs for more than 7 months were significantly higher than those of the pre- and postmenopausal subjects. These levels increased progressively with duration of OC use. These levels did not fluctuate with the menstrual cycle in either OC or non-OC users. Levels of erythrocyte selenium and plasma pyridoxal were not significantly altered by OC use. Riboflavin status, however, as estimated by glutathione reductase activity was substantially lower in OC users and was lowest in women who had used OCs for the longest amount of time. Riboflavin status was found to be directly correlated with erythrocyte glutathione peroxidase levels. These findings may be important because selenium is currently believed to offer protective benefits against carcinogenesis, especially breast cancer. All the OCs studied produced the same effects.

The effect of anti-cancer drugs on the plasma disposition of antipyrine and the biliary excretion of phenolphthalein in the rat.

Abstract The uptake and plasma disposition of antipyrine in the rat have been examined as a possible model for estimating the metabolic effects caused by the administration of the cytotoxic anti-cancer drugs to man. Pretreatment of the rats with the anti-cancer drugs retarded and decreased absorption from the stomach and the elimination of antipyrine from the plasma was also considerably decreased. In parallel with these findings the marked reeduction in the biliary excretion of phenolphthalein indicated a decrease in hepatic function caused by the cytotoxic drugs. In vitro investigations appeared to suggest the most likely cause of the prolonged antipyrine plasma half-life was the reduction in hepatic cytochrome P450 content.

The Effect of Chronic Alcohol Intake Upon the Hepatic Microsomal Carcinogen-activation System

Ethanol was administered to mice either by repeated intraperitoneal injection, or orally in the drinking water over an extended period of time. Following intraperitoneal ethanol pre-treatment further groups of mice received an injection of benzo(a)pyrene. Alcohol intake decreased the level of microsomal aryl hydrocarbon hydroxylase which corresponded to the observed decrease in DNA binding of benzo(a)pyrene. In contrast, the number of tumors which developed in the alcohol pre-treated mice exceeded those of the control animals.

An in vitro assessment of the effect of cytotoxic drugs upon the intestinal absorption of nutrients in rats

Abstract The effect of anti-cancer drug pretreatment on the rate of uptake of various 14C-labelled nutrients has been investigated using intestinal everted sac preparations. The cytotoxic drugs decreased the efficiency of the barrier to passive penetration of the intestine by the nutrients. The rate of uptake of all nutrients except monopalmitic acid was reduced by a decrease in active absorption. There was no significant difference in tryptophan uptake between methotrexate or 5-fluorouracil pretreated animals. It was concluded that cytotoxic drugs reduce intestinal absorption by inhibiting carriers involved in “active-transport” mediated uptake.

The Serum Levels of Some Trace and Bulk Elements in Cancer Patients

The levels of copper, zinc, calcium, manganese and magnesium have been monitored in the sera of patients suffering from various types of cancer. Only serum copper appeared to be of any diagnostic significance, its levels being above the normal reported range in the breast cancer, leukaemia and Hodgkins lymphoma patients. In the case of breast cancer, serum copper is progressively elevated according to the stage of the disease. Serum calcium levels were also significantly lower in patients with tumours of the breast, gastrointestinal tract and cervix. The results suggest that serum copper levels could be of prognostic significance in breast cancer patients receiving radiotherapy.

The effect of ethanol ingestion on the erythrocyte antioxidant defence systems of rats.

Abstract The effect of ingestion of water containing 1 or 10% ethanol for a period of four weeks on serum vitamin E, hepatic glutathione peroxidase, erythrocyte-glutathione peroxidase, glutathione transferase, Superoxide dismutase and selenium has been investigated in rats. The serum levels of total and free vitamin E were not significantly affected by ethanol ingestion at either level. The level of erythrocyte glutathione peroxidase was decreased to 43 or 28 per cent of the control level by intake of either 1 or 10% ethanol solution, respectively, whilst there was no alteration in glutathione transferase activity. Ethanol treatment did not alter erythrocyte selenium levels or Superoxide dismutase activity. Hepatic glutathione peroxidase activity was increased to approximately 166 per cent of the control value by either 1 or 10% ethanol ingestion. The results indicate that the activity of the enzyme principally involved in preventing lipohydroperoxide-induced haemolysis is significantly reduced by ethanol ingestion.

Serum Galactosyl Transferase Levels in Patients with Advanced Cancer

Serum galactosyl transferase was significantly higher in patients with various types of cancer than in age-matched controls. The highest serum enzyme levels were observed in the breast and respiratory cancer, followed by ovarian and gastrointestinal tumours; whereas the enzyme activity in prostatic cancer patients was not significantly higher than in the control subjects. In the cancer patients the serum levels of this enzyme were not significantly higher in the presence of metastases. In terminally ill patients, the serum enzyme activity decreased proportionately in accordance with the progression of their disease.

Correlation between Tumour Size, Metastatic Spread and Galactosyl Transferase Activity in Cyclophosphamide-Treated Mice Bearing the Lewis Lung Carcinoma

Galactosyl transferase activity was measured in tumour and normal tissues of mice receiving cyclophosphamide treatment for Lewis lung carcinoma. Animals which responded to cyclophosphamide therapy had significantly smaller tumours with fewer metastases than the untreated mice. The level of galactosyl transferase was significantly reduced in the tumours which were inhibited by the cyclophosphamide treatment.

The effect of chloroform ingestion on the growth of some murine tumours

Abstract Chloroform was administered to mice in their drinking water at a dose level of either 0.15 or 15 mg/kg/day. At the lower dose level chloroform did not significantly alter the rate of multiplication of the Ehrlich ascites cells. Prolonged intake of chloroform at 0.15 mg/kg significantly increased the Lewis lung tumour protein levels although the growth and metastasis in the chloroform-ingesting animals was not significantly different from the controls. The percentage of animals with organs invaded by B 16 melanoma was increased by chloroform ingestion at 0.15 mg/kg. At the higher treatment level the rate of metastasis of the Lewis lung carcinoma and the number of Ehrlich ascites cells were increased.

The Effect of Chronic Ethanol Intake on the Growth and Spread of Some Murine Tumors

The effect of chronic ethanol intake on the growth and spread of some murine tumors has been investigated. The treatment had no effect on the B 16 melanoma but tended to decrease the number of Ehrlich ascites cells. In the case of the Lewis lung carcinoma, administration of ethanol for two weeks tended to lower the number of metastases to the lung without significantly affecting the primary tumor size, whereas more prolonged ethanol intake decreased the weight of the primary tumor in addition to decreasing its dissemination.