CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study

CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A->G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A->G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95 percent CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95 percent CI = 0.70-2.79) with OSCC.

Changes in red blood cell osmotic fragility induced by total plasma and plasma fractions obtained from rats bearing progressive and regressive variants of the Walker 256 tumor

Two variants (A and B) of the widely employed Walker 256 rat tumor cells are known. When inoculated sc, the A variant produces solid, invasive, highly metastasizing tumors that cause severe systemic effects and death. We have obtained a regressive variant (AR) whose sc growth is slower, resulting in 70-80 percent regression followed by development of immunity against A and AR variants. Simultaneously with the beginning of tumor regression, a temporary anemia developed (about 8 days duration), accompanied by marked splenomegaly (about 300 percent) and changes in red blood cell osmotic fragility, with mean corpuscular fragility increasing from 4.1 to 6.5 g/l NaCl. The possibility was raised that plasma factors associated with the immune response induced these changes. In the present study, we identify and compare the osmotic fragility increasing activity of plasma fractions obtained from A and AR tumor bearers at different stages of tumor development. The results showed that by day 4 compounds precipitating in 60 percent (NH4)2SO4 and able to increase red blood cell osmotic fragility appeared in the plasma of A and AR tumor bearers. Later, these compounds disappeared from the plasma of A tumor bearers but slightly increased in the plasma of AR tumor bearers. Furthermore, by day 10, compounds precipitating between 60 and 80 percent (NH4)2SO4 and with similar effects appeared only in plasma of AR tumor bearers. The salt solubility, production kinetics and hemolytic activity of these compounds resemble those of the immunoglobulins. This, together with their preferential increase in rats bearing the AR variant, suggest their association with an immune response against this tumor

The hemolytic component of cancer anemia: effects of osmotic and metabolic stress on the erythrocytes of rats bearing multifocal inoculations of the Walker 256 tumor

Cancer anemia is classified as an anemia of chronic diseases, although it is sometimes the first symptom of cancer. Cancer anemia includes a hemolytic component, important in the terminal stage when even transfused cells are rapidly destroyed. The presence of a chronic component and the terminal complications of the illness limit studies of the hemolytic component. A multifocal model of tumor growth was used here to simulate the terminal metastatic dissemination stage (several simultaneous inoculations of Walker 256 cells). The hemolytic component of anemia began 3-4 days after inoculation in 100 percent of the rats and progressed rapidly thereafter: Hb levels dropped from 14.9 +/- 0.02 to 8.7 +/- 0.06 from days 7 to 11 (~5 times the physiologically normal rate in rats) in the absence of bleeding. The development of anemia was correlated (r2 = 0.86) with the development of other systemic effects such as anorexia. There was a significant decrease in the osmotic fragility of circulating erythrocytes: the NaCl concentration causing 50 percent lysis was reduced from 4.52 +/- 0.06 to 4.10 +/- 0.01 (P<0.01) on day 7, indicating a reduction in erythrocyte volume. However, with mild metabolic stress (4-h incubation at 37§C), the erythrocytes showed a greater increase in osmotic fragility than the controls, suggesting marked alteration of erythrocyte homeostasis. These effects may be due to primary plasma membrane alterations (transport and/or permeability) and/or may be secondary to metabolic changes. This multifocal model is adequate for studying the hemolytic component of cancer anemia since it is rapid, highly reproducible and causes minimal animal suffering.

The effect of dietary lipids on rat liver mithocondrial swelling

The swelling of liver mitochondria resulting from changes in the dietary fatty acid (FA) was investigated in rats fed two lipid diets for two or four months. Female Sprague-Dawley rats were fed two semi-synthetic and isocaloric diets. One diet (CO diet) contained 10 per cent coconut fat (rich in saturated fatty acids, SFA) while the other (SO diet) contained 10 per cent sunflower seed oil (rich in unsaturated fatty acids, UFA). The initial velocity (Vo) was used to determine the velocity of the spontaneous and phosphate - or calcium-induced sweeling of rat liver mitochondria. The changes in the fatty acid composition of the mitochondrial membranes were expressed as the unsaturation index, as well as the total content of saturated and unsaturated fatty acids and their ratios. The liver mitochondrial phospholipid fatty acid composition was very similar in both diet groups, in spite of the differences in dietary lipid fatty acid content. Only the 16:0, 16:1 (@-7) and 16:1 (@-9) fatty acids of the liver mitochondrial phospholipids differed significantly during the experiment. In general, the diets and the lenght of treatment had no significant influence on the extent of swelling. However, for animals fed the SO diet, significant differences in the for Vo of the phosphate - and calcium-induced swelling was observed. This result probably reflects greater fluidity of the mitochondrial membrane due to the high content of the fatty acid residues which would produce a more flexible and less stable membrane system

The effect of thyroidectomy on male rats fed two antagonist lipid diets. IV. The fatty acid content of mitochondrial lipids of heart and gastrocnemic muscles

The fatty acid (FA) contents of heart and gatrocnemic muscle mitochondrial lipids of thyroidecromized and control (sham-operated) were analyzed. Animals were fed either an n-6 polyunsaturated (PUFA)-rich diet A or an n- PUFA-rich diet B during 30 days. It was observed alteraions in the composition of FA of those cell organelles caused by the absence of the thyroid gland. Some of these alterations were dependent of the type of used diet. Thyroidecromy caused an increase of P?S ratio in heart and gastrocnemic muscle but only for animals fed diet B. Thyroidectomy caused an increase of n-6/n-3 ratio in heart of rats fed diet A and in gastrocnemic muscle of rats fed diet B and it caused a decrease of n-6/n-3 ratio of heart of rats fed diet A and in gastrocnemic muscle of rats fed diet B. The absence of thyroid gland in some way may interfer in the FA metabolism and in the rate of FA incorporation into endogeneous lipids but in a different process dependent of type of tissue and of used lipid diet

The effect of the thyroidectomy in male rats fed two antagonist lipid diets. V. The mitochondrial ATPase activity of heart and gastrocnemic muscles

The mitochondrial ATPase activity of heart and gastrocnemic muscles of thyroidectomized and control rats was determined. Some rats were fed an n-6 polyunsaturated fatty acids (PUFA)-rich diet A and others were fed an n-3PUFA-rich diet B, during 30 days. The heart mitochondrial ATPase activity of rats fed diet A was higher than of rats fed diet B in both thyroidectomized (p < 0.01) and control (p < 0.05) groups. The thyroidectomy induced an increase of heart mitochondrial ATPase activity in both dietary groups (p < 0.01). The thyroidectomy also induced an increase in gastrocnemic mitochondrial ATPase activity in diet B group, but it induced a decrease in ATPase activity in diet A group. The data suggest that the dietary lipids and the absence of thyroid gland induce changes in mitochondrial ATPase activity in heart and gastrocnemic muscles, confirming the same observations previously y described for the effect of thyroidectomy and diet in rat liver and brain (9)

Effect of the thyroidectomy on male rats fed two antagonist lipid diets: I. Physiological aspects

Male rats fed an n-6 polyunsaturated fatty acid (PUFA)-rich diet A or an n-3 PUFA-rich diet B were subjected to a surgical thyroidectomy or to a sham-operation (control animals). Thyroidectomy caused a lesser daily increase of body weight in both dietary groups. The diet A rats showed in average greater values of body weight than diet B rats, for control and thyroidectomized animals. After 30 days of experiment thyroidectomy caused no effect on the relative weight (g/100g body weight) of liver in both dietary groups. However, it increased the relative weight) of gastrocnemius (p<0.05) and brain (p<0.001) in both dietary groups, and it decreased the relative weight of heart in both dietary groups, and it decreased the relative weight of heart in diet A (NS) and in diet B (p<0.05) groups. The relative weights of heart, gastrocnemius, liver and brain of control and thyroidectomized rats of diet A groups were lower than respective organs of diet B groups. Thyroidectomy did not affect the level of plasma proteins of diet B rats was higher than diet A rats, for controls or thyroidectomized animals. Iodine uptake by thyroid gland, the plasma level of T3 of diet B control rats were significant higher thand diet A control rats, but the plasma level of T4 of diet A control rats was higher than diet B control rats (NS). These results suggested that the thyroidectomy and or lipid diets may alter the rat development as well the ingestion of antagonist lipid diets may alter thyroid gland functions

The effect of the thyroidectomy in male rats fed two antagonist lipid diets: II. The fatty acid content of lipids of plasma and mitochondria of liver and brain

Male rats subjected to surgicl thyroidectomy showed alteration in the content of fatty acids (FA) of plasma and mitochondria of liver and brain lipids in comparison to control animals (sham-operated). Those alterations depend of the kind of dietary fat intake. Control and thyroidectomized rats fed an n-6 polyunsaturated fatty acid (PUFA)-rich diet A or an n-3 PUFA-rich diet B. Thyroidectomy, independently of kind of diet, did not cause any alteration on the P/S ratio in plasma or brain mithocondria. However, it caused an increase on the P/S ratio in liver mithochondria, more evident in the dietary group B. This fact may suggest that the absence of thyroid hormones would induce a higher incorporation of PUFAs in liver lipids. Thyroidectomy caused a decrease of linoleic acid (LA) content in plasma of both dietary groups but it caused an increase of LA in diet A brain mitochondria groups. The plasma FA content, although depends on the source of fat intake, was not a mere reflection of the diet FA ingested. As the thyroidectomy also changed the content of plasma FA, it is possible to postulate that the plasma FA should be actually a reflection of the FA content of endogenous lipds

The effect of thyroidectomy in male rats fed two antagonist lipid diets: III. The liver and brain mitochondrial ATPase activity

The liver and brain mitochondrial ATPase activity of surgical thyroidectomized male rats fed two antagonist lipid diets, an n06 polyunsaturated fatty (PUFA)-rich diet A or an n-3 PUFA-rich diet B, during 30 days, was different in comparison to the respective controls (sham-operated animals). Thyroidectomy did not change the diet A liver and diet B brain ATPase activity, but it increased the diet B liver ATPase (p<0.001) and decreased the diet A brain ATPase (p<0.001). The ATPase activity was also altered in function of used diets, with the exception of thyroidectomized rats in liver. The ATPase of diet A control rats was higher than the enzyme of diet B control rats in liver (p<0.001) and brain (p<0.001). The ATPase of diet A thyroidectomized rats was higher than the diet B thyroidectomized rats ATPase (p<0.005)