Correspondence Re: Y. Fujimoto et al., Alterations of tumor suppressor genes and allelic losses in human hepatocellular carcinomas in China. Cancer Res., 54: 281-285, 1994.
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Aflatoxins↗
Biomedical subjects
T C Campbell
Publications and source records attributed to T C Campbell.
Bone density and lifestyle characteristics in premenopausal and postmenopausal Chinese women.
The relationships between bone health and various lifestyle factors were examined in a cross-sectional study in 775 Chinese women aged 35-75 years. Bone mass was significantly positively associated with body weight, height, body mass index (BMI) and duration of breastfeeding, but was not significantly associated with other lifestyle variables, including alcohol consumption, parity, age at menarche and age at menopause after adjusting for age and body weight. A positive association was observed in premenopausal women (but not in postmenopausal women) for bone density with current cigarette smoking and plasma and urinary cotinine (the major metabolite of smoking). However, the confounding effects of other unknown factors present in this cross-sectional study may not be excluded. Daily physical activity, as indicated by time spent working in the fields, was found consistently to be positively associated with bone mass (p < 0.0001). When these women were grouped into three physical activity levels on the basis of occupation and daily work intensity, those undertaking heavy labor also had significantly higher radial bone mass than women undertaking light or medium labor. These results suggest a protective effect of daily physical activity on bone health in both pre- and postmenopausal women.
Adult↗
Accuracy and reliability of total body electrical conductivity (TOBEC) for determining body composition of rats in experimental studies.
Total body electrical conductivity (TOBEC) has been promoted as a noninvasive method to estimate body composition in small mammals. Validation of this method has primarily been under normative conditions and has generally been inadequate. This article reports on the reliability and accuracy of TOBEC methodology to assess gradual, physiologically induced changes in body composition in rats under different experimental conditions. Reliability of the index of electrical conductivity (EM number) was assessed by analyzing components of variance. Accuracy was assessed by comparing EM number to actual lean body mass (LBM, from carcass analysis), across different experimental conditions, within a particular experimental condition, and over time for a given set of animals. Reliable measurements were obtained by strictly adhering to a standard protocol. TOBEC was inaccurate across experimental conditions, within experimental conditions, and within a single experimental condition during the course of an experiment. This inaccuracy apparently stemmed from the lack of a direct relationship between EM number and LBM; EM number was more strongly correlated with body weight than with LBM. At the present time, TOBEC cannot be used in place of carcass analysis to accurately predict the body composition of rats during or following the administration of a variety of experimental conditions.
Adipose Tissue↗
Diet and chronic degenerative diseases: perspectives from China.
A comprehensive ecologic survey of dietary, life-style, and mortality characteristics of 65 counties in rural China showed that diets are substantially richer in foods of plant origin when compared with diets consumed in the more industrialized, Western societies. Mean intakes of animal protein (about one-tenth of the mean intake in the United States as energy percent), total fat (14.5% of energy), and dietary fiber (33.3 g/d) reflected a substantial preference for foods of plant origin. Mean plasma cholesterol concentration, at approximately 3.23-3.49 mmol/L, corresponds to this dietary life-style. The principal hypothesis under investigation in this paper is that chronic degenerative diseases are prevented by an aggregate effect of nutrients and nutrient-intake amounts that are commonly supplied by foods of plant origin. The breadth and consistency of evidence for this hypothesis was investigated with multiple intake-biomarker-disease associations, which were appropriately adjusted. There appears to be no threshold of plant-food enrichment or minimization of fat intake beyond which further disease prevention does not occur. These findings suggest that even small intakes of foods of animal origin are associated with significant increases in plasma cholesterol concentrations, which are associated, in turn, with significant increases in chronic degenerative disease mortality rates.
China↗
Assessment of a modified household food weighing method in a study of bone health in China.
OBJECTIVE: A 'modified' household dietary method to estimate individual intakes from total household intakes was evaluated in comparison to the individual food weighing method, i.e. direct weighing of foods consumed by individuals. DESIGN: Foods consumed by the household were weighed and recorded over a 3 day period and were proportionally allocated to a specific person in the household by using energy conversion factors based on age, gender and physical activity. The individual dietary intakes were standardized by body weight (ratio of individual body weight to reference body weight from Chinese Recommended Daily Allowances (Acta Nutr. Sin. 12, 1-9), and were compared with the estimates from the individual food weighing method for both accuracy and associations with bone density. SETTING: The subjects were randomly selected from five rural countries in China, characterized by different dietary patterns. SUBJECTS: A total of 712 women aged 35-75 years participated in the dietary and bone measurements. RESULTS: Nutrient intakes estimated by the modified household method (adjusting for body weight were very similar to those obtained by the individual method (r = 0.53-0.78, P < 0.001), except for sodium which had the largest deviation from the individual methods (r = 0.23, P < 0.001). Calcium intakes were 405 +/- 271 and 409 +/- 323 mg/day, respectively, as estimated by the individual and modified household methods. A very similar degree of correlation with radial bone density also was obtained for both calcium estimates. CONCLUSION: The results indicate that the modified household method is appropriate for assessing food intakes of individuals in large nutritional studies.
Adolescent↗
Correspondence re: G-S. Qian, et al., A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People's Republic of China. Cancer Epidemiol., Biomarkers & Prev., 3:3-10, 1994, and C.C. Harris, Solving the viral-chemical puzzle of human liver carcinogenesis. Cancer Epidemiol., Biomarkers & Prev., 3:1-2, 1994.
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Aflatoxins↗
Geographic association between urinary excretion of N-nitroso compounds and oesophageal cancer mortality in China.
Overnight urine samples were collected from approximately 60 male adults in each of 69 counties of China in 1989. Two specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids and nitrate were measured in urine samples and correlated with cumulative mortality rates for subjects aged between 0 and 64 years in the 1970s. Oesophageal cancer mortality rates were positively and significantly associated with (i) urinary levels of excreted N-nitrosoproline (NPRO) (after proline and ascorbic acid loading or proline loading only), (ii) N-nitrososarcosine levels, and (iii) nitrosation potential (the decrease in the amount of urinary NPRO after adding ascorbic acid to the proline load). There were also positive correlations between the urinary level of NPRO or other N-nitrosamino acids and that of nitrate. The urinary excretion of nitrate was associated with consumption of various nitrate-rich vegetables. The results suggest that N-nitroso compounds (NOC) or other nitrite-derived carcinogens are implicated in the aetiology of oesophageal cancer in China.
Adult↗
Dietary calcium and bone density among middle-aged and elderly women in China.
Associations between dietary calcium and bone status were investigated in 843 Chinese women aged 35-75 y who were selected from five rural counties where dietary calcium varied considerably. Bone mineral content (BMC) and bone mineral density (BMD) at the radius were significantly higher in one of the pastoral counties with higher calcium intake than in the nonpastoral counties. Analysis by individual for all counties combined showed that BMC and BMD were correlated positively with total calcium (r = 0.27-0.38, P < 0.0001), dairy calcium (r = 0.34-0.40, P < 0.0001), and to a lesser extent with nondairy calcium (r = 0.06-0.12, P = 0.001-0.100), even after age and/or body weight were adjusted for. The results strongly indicated that dietary calcium, especially from dairy sources, increased bone mass in middle-aged and elderly women by facilitating optimal peak bone mass earlier in life.
Adult↗
Dietary intakes and urinary excretion of calcium and acids: a cross-sectional study of women in China.
The relationship between dietary intakes and urinary calcium was examined in a cross-sectional survey of 764 middle-aged and elderly women with markedly different dietary patterns and lifestyles. Urinary calcium was correlated positively with urinary acids, including titratable acid (r = 0.46, P < 0.0001), ammonia (r = 0.42, P < 0.0001), and sulfate (r = 0.52, P < 0.0001). Urinary excretions of calcium and acids were correlated positively with intakes of animal and nondairy animal protein but were correlated negatively with plant-protein intake, possibly because of the alkaline nature of plant foods. Further analyses showed that urinary calcium and acids were associated positively with acid-forming foods and were associated negatively with plant foods. These results indicate that under free-living conditions urinary calcium excretion is likely determined by the acid-base status of the total diet, including among other factors the contribution of sulfur amino acids to urinary acid production.
Acids↗
The effects of D-fenfluramine on the development of aflatoxin-B1 induced GGT+ hepatic foci in F344 rats.
The role of total caloric intake and attained body weight in the carcinogenic process in rodents is controversial. In the present study we examined the development of hepatic pre-neoplastic foci in rats treated with aflatoxin-B1 (AFB) and given the drug D-fenfluramine (FEN). Ingestion of this drug leads to a reduction in body weight by increasing the thermogenic response to a meal and by transiently reducing food intake. Young male rats were dosed with AFB or vehicle alone and were then assigned to receive control diet (NO FEN) or control diet + FEN (FEN; 0.15 g/kg diet) for 12-14 weeks. Body weight gain and food intake were reduced among animals given FEN; brown adipose tissue weight (% body weight) was elevated in these groups. Indices of protein status, and concentrations of T3, T4 and insulin did not differ among the groups. All animals given FEN developed GGT+ hepatic foci. The number and volume fraction of foci were significantly larger in FEN relative to NO FEN animals. The mean diameter of foci was slightly enhanced among FEN animals. These results suggest that FEN promotes the development of AFB-induced hepatocellular foci, despite reduced food intake and lower body weight. Since FEN is widely used as a weight loss aid, these findings deserve further study.
Adipose Tissue↗
Attenuation of preneoplastic lesion development by dietary protein intervention: apparent persistence and regression.
The effects of feeding high protein diets that promote the development of aflatoxin B1 (AFB1)-induced gamma-glutamyl transpeptidase positive (GGT+) preneoplastic lesions were examined in Fischer 344 (F344) rats. After administering AFB1 for 2 weeks (initiation), animals were fed diets over four successive 3-week periods (promotion). Either a low (5% casein) or high (20% casein) protein diet was fed for 3, 6, or 9 weeks before switching to the opposite diet to determine whether progressively longer periods of feeding the initial diet caused preneoplastic foci to become more refractory to the intervention effects of the second diet. The results from animals consuming the 20% casein diet for progressively longer periods suggest that longer exposure to the high protein diet progressively enhances the potential for future lesion growth. Results from animals consuming the 5% casein diet for progressively longer periods suggest that longer exposure to the inhibitory low protein diet progressively inhibits the potential for future lesion growth. These results suggest that a high protein diet is a potent promoter of preneoplastic growth and that progressively longer exposure to a particular promotive environment increasingly attenuates foci response to future dietary intervention.
Animals↗
Additional ecological evidence: lipids and breast cancer mortality among women aged 55 and over in China.
That dietary fat increases breast cancer risk has been strongly supported by international data collected among developed countries during the past few decades. Population aggregates with elevated lipid intake have tended to report elevated breast cancer incidence and mortality. This study is an ecological analysis of the association of various indicators of lipid intake with breast cancer mortality in 65 county-wide population aggregates in the People's Republic of China. Although the result is consistent with a positive association between lipid intake and breast cancer risk, the observed association is weaker than the association previously observed. This finding provides only modest support for the possibility of a diet-breast cancer link.
Aged↗
The sustained development of preneoplastic lesions depends on high protein intake.
The effects of sequential alterations in the feeding of two levels of dietary protein (5% and 20% casein) on the postinitiation development of aflatoxin B1- (AFB1) induced gamma-glutamyl transpeptidase-positive (GGT+) preneoplastic foci were examined. Weanling male Fischer 344 rats fed AIN-76A diet (20% protein) were administered 10 intragastric doses of AFB1 (1 dose/day during the 14-day dosing period excluding weekends) at 250 micrograms/kg body wt (initiation). After AFB1 tissue clearance, rats were randomly assigned to dietary treatment groups. During the next 12 weeks (promotion), they developed AFB1-induced GGT+ preneoplastic lesions. The 12-week promotion period was subdivided into four three-week periods, during which rats were fed isocaloric diets containing 20% casein during all four periods (20:20:20:20), 5% casein during all four periods (5:5:5:5), or sequentially altered casein levels (20:5:20:5 and 5:20:5:20). Rats were killed at 3,6,9, and 12 weeks to examine the dependence of GGT+ foci development on protein intake. Animals fed 5% casein diets developed significantly fewer (p < 0.01) GGT+ foci than animals fed 20% casein diets despite greater total caloric intake. Similarly, in the intervention groups, preneoplastic development was enhanced when the 20% casein diet was fed and inhibited when the 5% casein diet was fed. These results indicate that the sustained development of AFB1-induced preneoplastic foci depends on a high protein intake. Alternatively, these results suggest that low protein intake inhibits lesion development.
Aflatoxin B1↗
Inhibition of aflatoxin B1-induced gamma-glutamyltranspeptidase positive (GGT+) hepatic preneoplastic foci and tumors by low protein diets: evidence that altered GGT+ foci indicate neoplastic potential.
Previous studies in this laboratory with young Fischer 344 male rats have shown that the post-initiation development of aflatoxin B1 (AFB1)-induced gamma-glutamyltranspeptidase positive (GGT+) hepatic foci was markedly inhibited by low protein feeding, even though the energy intake was greater. This dietary effect, however, did not necessarily apply to hepatic tumor development. Thus, the present investigation was undertaken to examine this dietary effect upon the development of hepatic tumors and, is so doing, to determine the correlation of foci development with tumor development. Following AFB1 dosing (15 daily doses of 0.3 mg/kg each), animals were fed diets containing 6, 14 or 22% casein (5.2, 12.2, 19.1% protein) for 6, 12, 40, 58 and 100 weeks. Foci at 12 weeks and tumors at 40, 58 and 100 weeks developed dose-dependently to protein intake. Foci development, tumor incidence, tumor size and the number of tumors per animal were markedly reduced while the time to tumor emergence was increased with low protein feeding. Non-hepatic tumor incidence also was lower in the animals fed the lowest protein diet. Foci development indices (foci number, per cent liver volume occupied) were highly correlated with tumor incidence at 58 and 100 weeks (r = 0.90-1.00). Tumor and foci inhibition occurred in spite of the greater energy intake.
Aflatoxin B1↗
Antioxidant status and cancer mortality in China.
Sex-specific mortality rates for selected cancer sites (including oesophagus, stomach, liver, lung, colorectum, breast and cervix) and a variety of biochemical indicators of antioxidant status, enzyme activity and oxidative stress (including plasma levels of beta-carotene, alpha-tocopherol, ascorbic acid, selenium, glutathione peroxidase, catalase, superoxide dismutase, iron, copper, zinc, total cholesterol and lipid peroxide) were examined in an ecological study of 65 mostly rural counties in the People's Republic of China. The wide range of both mortality rates and biochemical values and the measurement of a comprehensive set of biochemical indicators permitted both simple correlational and multivariate analyses of the joint and relative effects of each factor on site-specific cancer mortality. Plasma levels of dietary antioxidants were consistently negatively correlated with cancer mortality rates. Ascorbic acid was most strongly negatively associated with most cancers and selenium with oesophageal and stomach cancers. beta-carotene was found to have a protective effect independent of retinol, particularly for stomach cancer.
Adult↗
Associations between breast cancer, plasma triglycerides, and cholesterol.
A case-control study investigating the association between plasma lipids and breast cancer was conducted among women aged 30-80 in Buffalo, NY. All eligible women from a large breast clinic and two area physicians' offices were requested to participate over a one-year period. Subjects completed a health questionnaire and donated a fasting blood sample prior to diagnostic breast biopsies. The 83 women found to have breast cancer (cases) had significantly higher plasma triglyceride values than did the 113 women found not to have breast cancer (controls). Lower plasma beta-carotene values were associated with breast cancer, but only in those women with elevated triglyceride or cholesterol. Plasma cholesterol values were lower in those breast cancer cases presenting with more advanced stages of cancer, suggesting that metabolic effects of clinical and preclinical breast cancer may lower cholesterol levels. Although the limitations of case-control studies are well-recognized, these data suggest an etiologic role for plasma triglycerides and beta-carotene or for related dietary factors.
Adult↗
Thermogenesis, low-protein diets, and decreased development of AFB1-induced preneoplastic foci in rat liver.
The development of hepatocellular, putatively preneoplastic, gamma-glutamyl transpeptidase positive (GGT+) foci and tumors induced by aflatoxin B1 (AFB1) has been shown to be reduced in male F344 rats fed a diet containing 6% protein (as casein). This reduction occurs despite increased energy intake, when compared with animals fed a diet containing 22% protein. Among its many effects, low protein intake is known to increase the proportion of energy intake expended in the form of heat (thermogenesis); thus, this investigation examined the association between the development of GGT+ foci and alterations in indices of thermogenesis induced by feeding varying levels of dietary protein. Five days following the completion of AFB1 dosing, animals were assigned to groups fed 4%, 8%, 12%, 16%, or 22% dietary protein for 6 weeks. Foci development (% liver volume occupied) was markedly reduced in animals fed the low-protein diet (4%, 8%), yet calorie consumption per 100 g body wt was greater. A modest negative linear trend was observed in oxygen consumption with increasing levels of dietary protein intake. Urinary norepinephrine levels were elevated in the groups fed 4% and 8% protein; urinary dopamine and norepinephrine turnover rates in brown adipose tissue were highest in animals fed 4% protein. These results suggest that GGT+ foci development occurs when a "critical level" (approx 12%) of dietary protein intake is reached. Inhibition of foci development at lower levels of protein intake is associated with several indicators of increased thermogenesis.
Aflatoxin B1↗
High protein intake promotes the growth of hepatic preneoplastic foci in Fischer #344 rats: evidence that early remodeled foci retain the potential for future growth.
The effects of successive administration, withdrawal and readministration of high protein diets (20% casein) on the promotional growth, remodeling and regrowth of aflatoxin B1-induced preneoplastic liver lesions (foci) were examined. Weanling male Fischer 344 rats were given 10 intragastric doses of aflatoxin B1 at a level of 250 micrograms/kg body weight over a 2-wk dosing period (initiation). The subsequent 12-wk period was subdivided into four feeding periods, each lasting 3 wk (promotion). Two groups of rats were fed either a 20 or 5% casein diet during all four periods; additional groups were alternately fed these diets in different sequences. Switching from the high protein diet to a low protein diet (5% casein) resulted in marked remodeling (regression) of the growing lesions to a response level similar to that in animals that did not receive the initial promotional stimulus of high protein feeding. However, refeeding the high protein diet caused significant reappearance of these lesions. The restimulated development of these remodeled lesions far exceeded lesion growth in animals receiving only the late promotional stimulus of high dietary protein. Thus, these data suggest that a second occurrence of high protein feeding promotes the growth of remodeled foci, thus demonstrating their potential for future promotional growth.
Animals↗