Chemical carcinogenesis and chemoprevention: Scientific priority area in rapidly industrializing developing countries

Occupational cancers are now a serious concern in industrializing developing countries where exposure levels to hazardous chemicals considerably exceed regulatory limits established in industrialized countries. The association between increasing use of chemicals and associated disorders and chemoprevention or anticarcinogenesis is insufficiently recognized in these countries. The eradication of chemicals would assist in cancer prevention. This is however, not pragmatic, thus the need to seek alternative means of cancer prevention. Cancer chemoprevention or anticarcinogenesis is the process of exposure of an animal including humans to a substance that will reduce the incidence of cancer that would otherwise develop. Lack of knowledge of the multiple pathways by which chemically induced cancer may arise has led to the erroneous view for a long time that the study of chemoprevention was academic. While this field is gaining an increasing and sustained attention in the developed countries it has received little attention in the industrializing developing countries where the incidence of cancers appears to parallel the pace of industrialization. Sub-optimal intake of specific micronutrients so common in developing countries may contribute to greater susceptibility to cancer. Micronutrient deficiency disorders (MDDs) is considered orders of magnitude more important than radiation because of constancy of exposure to a milieu promoting DNA damage. Zinc (Zn) for instance is an antioxidant, a component of p53 and a critical factor in gene expression. Poor Zn nutrition may be an important risk factor in oxidant release and development of DNA damage and cancer. A deficiency of Zn ranks among the top ten leading causes of death in developing countries. As chemo preventive agents are present in natural human foods abundant in developing countries, this should be one of the highest research priorities of the rapidly industrializing developing countries.Key words: Chemical carcinogenesis, chemoprevention, DNA damage, oxidative stress, Industrialization, p53protein, mutation

High cadmium / zinc ratio in cigarette smokers: potential implications as a biomarker of risk of prostate cancer.

Tobacco smoke may be one of the most common sources of cadmium (Cd) in the general population, particularly in the rising population of smokers in developing countries. Although a relationship between bothcigarette smoking and environmental Cd contamination with prostate cancer exist, the mechanisms are unclear. Most prospective cohort studies found a positive association between current smoking and a fatal cancer of the prostate. We investigated the interaction between zinc and cadmium and the potential risk of prostate cancer insmokers. Serum cadmium level was significantly (

Biochemical and histologic presentations of female wistar rats administered with different doses of paracetamol/methionine

Summary: This study was carried out to compare the hepatoprotective effect of methionine on paracetamol treated rats at both the peaks of toxicity and absorption. Female Wistar rats were divided into 17 groups consisting of eight rats per group and treated with different doses of paracetamol/methionine (5:1). Each control rat received 5 ml of physiologic saline. The study was terminated at two different end points –the 4th & 16th hours. Results show that rats administered with toxic doses (1000 mg/kg; 3000 mg/kg; 5000 mg/kg BW) of paracetamol exhibited significant increases (p<0.05) in the levels of ALT, AST, γ- GT compared with controls. These increases were much higher at the 16th than 4th hour but serum total protein, albumin and globulin were significantly decreased (p<0.05) by the end of the 16th hour. Histology results of rats in the 3000 & 5000 mg/kg (by the end of the 16th hour) confirmed hepatic damage; light microscopic evaluation of liver showed remarkable centrilobular necrosis. Moreover, the presence of mononuclear cells in liver section of rats intoxicated with APAP (5000 mg/kg) suggests a possible involvement of inflammatory process which resulted in regurgitation of bilirubin leading to its elevated level as well as increase activity of ALP. The hepatoprotective effect of methionine, on the other hand, was demonstrated in these rats at the 4th & 16th hours, and both results were comparable and therefore not significantly different (p>0.05) but elevation in GGT level still persisted. In conclusion, data obtained from this study suggest that these agents may be capable of inducing GGT, although further study is required to establish a possible relationship between methionine and this enzyme in some other animal species

Molecular epidemology: a better approach for the early detection of pathophysiologic response to environmental toxicants and disease

Our environment is becoming increasingly contaminated by a profusion of substances in the form of industrial and Municipal Waste, air and water pollutants; by heavy metals (such as lead) herbicides, pesticides, cosmetics and so on. The number of chemicals that affect man increases at alarming rates. These agents may be dangerous because they produce biochemical, genetic, structural or physiological lesions in a significant segment of the population. The importance of elucidating the nature and the mechanisms of physiological and toxicological reactions has been emphasized in the investigations of occupational and environmental diseases, such investigations have revealed that the clinical manifestations of intoxication may have their origin in injurious effects of subcellular or biochemical types. Slight to moderate derangements in metabolism may impair the functional activity of organs and lead to subclinical or overt clinical effects. These may elude detection or recognition of their health implications unless biomarkers, the functional components of molecular epidemiology are employed. Molecular epidemiology is an approach which aims to examine aetiology of disease in a more precise way by focusing on biomarkers of disease risk rather than relying on the actual occurrence of disease. Such studies can be carried out in a short time and with relatively small numbers of subjects compared with conventional epidemiology, which though currently more popular merely reveals association, and causal links often remain obscure. Detection of early biochemical lesions that are related to subsequent changes in structure and physiology would be useful as early indicators of environmental hazards that produce disease in humans, that is by employing molecular epidemiology. This will be greatly enhanced by newer tools, such as toxicogenomics and metabonomics

Molecular epidemology: a better approach for the early detection of pathophysiologic response to environmental toxicants and disease

Our environment is becoming increasingly contaminated by a profusion of substances in the form of industrial and Municipal Waste, air and water pollutants; by heavy metals (such as lead) herbicides, pesticides, cosmetics and so on. The number of chemicals that affect man increases at alarming rates. These agents may be dangerous because they produce biochemical, genetic, structural or physiological lesions in a significant segment of the population. The importance of elucidating the nature and the mechanisms of physiological and toxicological reactions has been emphasized in the investigations of occupational and environmental diseases, such investigations have revealed that the clinical manifestations of intoxication may have their origin in injurious effects of subcellular or biochemical types. Slight to moderate derangements in metabolism may impair the functional activity of organs and lead to subclinical or overt clinical effects. These may elude detection or recognition of their health implications unless biomarkers, the functional components of molecular epidemiology are employed. Molecular epidemiology is an approach which aims to examine aetiology of disease in a more precise way by focusing on biomarkers of disease risk rather than relying on the actual occurrence of disease. Such studies can be carried out in a short time and with relatively small numbers of subjects compared with conventional epidemiology, which though currently more popular merely reveals association, and causal links often remain obscure. Detection of early biochemical lesions that are related to subsequent changes in structure and physiology would be useful as early indicators of environmental hazards that produce disease in humans, that is by employing molecular epidemiology. This will be greatly enhanced by newer tools, such as toxicogenomics and metabonomics

Decreased total and ionized calcium levels and haematological indices in occupational lead exposure as evidence of the endocrine disruptive effect of lead

The multisystem and prime environmental and occupational toxin, lead (Pb) is seldom included in the list of endocrine disruptors group like bisphenols A, B and F, nonylphenol, benzoquine, equiline etc. One hundred and thirty-seven subjects consisting of 86 lead workers and 51 unexposed individuals (as controls) participated in the study. Dietary intake including dairy products and micronutrients as assessed by 24-hour dietary recall was similar between lead workers and controls. Calcium homeostasis and haematological indices were evaluated in all subjects. Blood lead level was significantly higher in the lead workers than in controls (P<0.001). Total and ionized calcium levels were in contrast significantly decreased in lead workers compared with controls (P<0.01, P<0.001 respectively). Inorganic phosphate level though slightly raised compared to controls did not reach statistical significance (P>0.05). The haematological indices, haemoglobin, haematocrit, and mean cell haemoglobin concentration like calcium levels were all significantly reduced (P<0.001) in all cases. Semi-quantitative assessment of erythrocyte protoporphyrin was trace (±) in both lead workers and controls (i.e. similar). Serum copper level was significantly higher in Pb workers than in controls (P<0.005). These decreases are consistent with a repression of the endocrine systems regulating both erythropoiesis and calcium homeostasis resident in the proximal convoluted tubule(PCT) of the kidney; the most vulnerable site to Pb damage. Our findings therefore, appear to provide evidence or a reminder that Pb satifies the conditions defining EDCs and should be recognized as one, especially in developing countries where high environmental Pb and malnutrition co-exist and may magnify this effec

Observations on the Haematopoietic systems in tropical lead poisoning

The Haemopoietic system was one of the earliest principal targets of lead (Pb) to be recognized and intensely studied but largely from temperate developed countries. This study reports investigations into the haemotobiochemical variations associated with occupational Pb poisoning in a tropical developing country. One hundred and thirty seven (137) subjects comprising 86 lead workers and 51 appropriately matched controls were studied. The lead workers all males included battery workers, home and autopainters, automechanics, welders, gasoline dispensers and ceramic workers. They were classified according to exposure categories based on the prevailing air lead level (PbA) at the occupational environment. Blood lead (PbB) was significantly higher in lead workers than in controls (P<0.001). the PbB of controls (occupationally unexposed) was also significantly higher than in communities that have either reduced or eliminated lead from petrol. Erythrocyte protoporphyrin (EPP) and prophobilinogen (PBG) were similar in lead workers and controls. The haem degradative product bilirubin was unlike EPP and PBG higher in controls (P<0.05). Indices of iron (Fe) homeostasis, serum Fe, total iron binding capacity (TIBC), transferrin, and percentage Fe saturation did not differ between lead workers and control (P>0.05) in all cases. There was also no alteration in RNA inetabolism as indicated by the absence of basophilic stippling in the erythrocytes of lead workers. Some indices of erythropoietic activity Hb, PCV and MCHC were all significantly decreased in lead workers, compared with controls (P<0.001) in all cases. In contrast, the haem cofactor metals, copper (Cu) and zinc (Zn) levels were significantly elevated in lead workers compared with controls (P<0.01; P<0.001) respectively. There was no variation with exposure category. These complex observations may suggest the interplay of acute phase and antioxidant responses of Cu in caeruloplasmin and Copper-Zinc supper oxide dismutase (Cu-Zn SOD) as well as the inhilation ('supplementation') of Zn fume from the occupational environment. This synergy appears to have significantly restored the activity of the major haem pathway enzyme, d-aminolaevulinate dyhydratase (ALA-D) a Zn dependent enzyme that is exquisitely inhibited by Pb. Thus modulating the deleterious effect of Pb on the haemopoietic system. These observations imply that the combination of the well known Zn deficiency in many tropical countries and the substantial environmental lead pollution may predispose the general population to a significantly depressed haemopoietic system. This may in turn increase the prevalence of subclinical or oven anaemia of 'uncertain' aetiology in the presence of other haem pathway stressors such as malnutrition

Effects of Methionine Containing Paracetamol Formulation on Serum Vitamins and Trace Elements in Male Rats

Methionine is an effective antidote in the treatment of paracetamol-induced toxicity but at large doses it has been reported to induce or aggravate a number of pathological conditions. It also alters plasma levels of many vital elements and molecules. This study was designed to identify if the alteration observed for antioxidant vitamins and minerals especially at sub-toxic and toxic levels of exposure in our earlier study of 24-hour exposure period may warrant trace elements supplementation. This was investigated by carrying out a 48-hour study to test the ability of a living organism to restore homeostasis of these vital molecules and elements. The levels of antioxidant minerals and vitamins were estimated in the serum samples obtained from adult male Wistar rats exposed to paracetamol tablets. At 100 mg\kg BW (body weight) vitamin A, niacin, riboflavin, selenium and manganese were not significantly different from the control group (p>0.05). Moreover at 350 mg\kg, all these indices except zinc were not significantly different in the exposed group compared with controls (p>0.05) whereas at 1000 mg\kg level of exposure manganese, selenium and vitamin E were not significantly decreased at the end of 48 hours of exposure but copper, niacin and vitamin A were significantly increased in the exposed group compared with the controls (p<0.05). These results suggest that with time the body may be capable of bringing about restoration of the levels of some of these elements\vitamins. This was more evident at 350 mg\kg level of exposure than a higher dose of 1000 mg\kg level