Effects of paraquat on anti-oxidant system in rats.

The toxic effects of paraquat on the anti-oxidant defense system of male albino rats were evaluated, after administering either a single dose (1.5 and 7.5 mg/kg of body weight) or continuous daily doses (same as above, i.e., 1.5 mg/kg and 7.5 mg/kg of body weight) for 3 and 7 days. Glutathione levels in blood cells, liver, lung and kidney tissues decreased in a dose and time dependent manner. Glutathione reductase and glucose-6-phosphate dehydrogenase activity decreased, whereas the activity of glutathione-S-transferase, glutathione peroxidase, catalase and superoxide dismutase increased in paraquat exposure. Malondialdehyde formation also increased in a dose and time dependent manner. The alterations of anti-oxidant system particularly glutathione can be utilized as biomarkers during management of paraquat poisoning.

Environmental contaminants in pathogenesis of breast cancer.

This review is an attempt to comprehend the diverse groups of environmental chemical contaminants with a potential for pathogenesis of breast cancer, their probable sources and the possible mechanisms by which these environmental contaminants act and interplay with other risk factors. Estrogens are closely related to the pathogenesis of breast cancer. Oxidative catabolism of estrogen, mediated by various cytochrome P450 enzymes, generates reactive free radicals that can cause oxidative damage. The same enzymes of estrogenic metabolic pathways catalyze biological activation of several environmental (xenobiotic) chemicals. Xenobiotic chemicals may exert their pathological effects through generation of reactive free radicals. Breast tissue can be a target of several xenobiotic agents. DNA-reactive metabolites of different xenobiotic compounds have been detected in breast tissue. Many phase I and II xenobiotic metabolizing enzymes are expressed in both normal and cancerous breast tissues. These enzymes play a significant role in the activation/detoxification of xenobiotic and endogenous compounds including estrogens. More than 30 carcinogenic chemicals are present in tobacco smoke; many of them are fat-soluble, resistant to metabolism and can be stored in breast adipose tissue. Similarly, pesticides are also known to cause oxidative stress; while some act as endocrine disruptor, some are shown to suppress apoptosis in estrogen sensitive cell lines. Reports have shown an association of smoking (both active and passive) and pesticides with breast cancer risk. However, the issues have remained controversial. Different mutagenic substances that are generated in the cooking process e.g., heterocyclic amines and polycyclic aromatic hydrocarbons (PAHs) can be a threat to breast tissue. PAHs and dioxins exert their adverse effects through the aryl hydrocarbon receptor (AhR), which activates several genes involved in the metabolisms of xenobiotic compounds and endogenous estrogens. These chemicals also induce AhR-dependent mitochondrial dysfunction. Many of the environmental pollutants suppress the immune system, which are implicated to risk. A better understanding about the biological effects of different environmental carcinogenic compounds and determination of their impact on rising incidence of breast cancer will be beneficial in improving preventive policy against breast cancer.

Adrenocorticotropic hormone production in breast cancer.

Presence of adrenocorticotropic hormone (ACTH) was investigated in tissues from 150 cases of primary breast cancer. ACTH peptides were detected in 16.7% cases and ACTH expression was higher in post-menopausal cancers. A significant association was noticed between the presence of ACTH and the positive estrogen receptor (ER) status of tumors. The study indicated a probable role of these ectopic ACTH peptides in steroid hormone related pathology of breast cancer.

Cancer preventive role of selected dietary factors.

Dietary behavior seems to be an important modifiable determinant for the risk of cancer. The evidences from several epidemiological studies suggest that higher intakes of fruits and vegetables have been associated with lower risk of cancer. Dietary phenolic and polyphenolic substances, terpenoids, dietary fibers, fish oils, some micronutrients present in foods of both plant and animal origin, and a reduction of caloric intake appear to inhibit the process of cancer development. Many dietary factors possess antioxidant and anti-inflammatory properties and cause induction of phase II enzymes like glutathione-S-transferases. It has been suggested that cruciferous vegetables play an important role in cancer prevention, and their chemopreventive effects are due to high glucosinolate content which under enzymatic hydrolysis produces bioactive compound isothiocyanates. Further, isothiocyanates of a wide variety of cruciferous vegetables are powerful inhibitors of carcinogenesis in experimental animal models. Several flavonoids present in fruits, tea, soya beans, etc. may be useful as cancer preventive agents. Similarly, ellagic acid, perillyl alcohol and resveratrol found in various fruits may have chemoprotective effect. Moreover, different vanilloids such as curcumin and gingerol have been shown to possess antioxidative properties. Nevertheless, in spite of several studies, still the effects of various ingredients are not clearly distinguished. In human, little convincing evidence has been established for the proposed protective effects of dietary constituents. It is an important future research goal to provide necessary evidences to support the chemopreventive role of different dietary factors, and also to clarify misunderstandings in this perplexing area.

Overexpression of c-erbB-2 oncoprotein and associated pathobiological factors in invasive primary breast cancer.

Breast cancer tissues from 271 cases were analyzed immunologically for c-erbB-2 oncoprotein (HER-2/neu), epidermal growth factor receptor (EGF-R) and estrogen receptor (ER). Overexpression of both c-erbB-2 oncoprotein and EGF-R showed an inverse association with ER and a direct association with metastatic involvement of lymph node and high histological grade. The frequency of c-erbB-2 and EGF-R overexpression was significantly higher among postmenopausal cases in comparison with premenopausal cases. Further, only in postmenopausal patients, c-erbB-2 oncoprotein (chi2 = 6.4, P < 0.05) and EGF-R (chi2 = 6.4, p < 0.05) as well as their concomitant expression (chi2 = 11.5, p < 0.01) revealed a statistically significant association with ER.