Search PubMed⌕ Search

Biomedical subjects

T C Campbell

Publications and source records attributed to T C Campbell.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Nonassociation of aflatoxin with primary liver cancer in a cross-sectional ecological survey in the People's Republic of China.

A comprehensive cross-sectional survey was undertaken in The People's Republic of China of possible risk factors for primary liver cancer (PLC) to include 48 survey sites, an approximately 600-fold aflatoxin exposure range, a 39-fold range of PLC mortality rates, a 28-fold range of hepatitis B virus surface antigen (HBsAg+) carrier prevalence, and estimation of exposures for a large number of other nutritional, dietary, and life-style features. PLC mortality was unrelated to aflatoxin intake (r = -0.17) but was positively correlated with HBsAg+ prevalence (P less than 0.001), plasma cholesterol (P less than 0.01), frequency of liquor consumption (P less than 0.01), and mean daily intake of cadmium from foods of plant origin (P less than 0.01). Multiple regression analyses for various combinations of risk factors showed that aflatoxin exposure consistently remained unassociated with PLC mortality regardless of variable adjustment. In contrast, associations of PLC mortality with HBsAg+, plasma cholesterol, and cadmium intake remained, regardless of model specification, while the association with liquor consumption was markedly attenuated (was nonsignificant) with adjustment for plasma cholesterol. The sharp contrast between the findings of no aflatoxin effect upon PLC prevalence in this survey and the positive correlation reported for previous but more restricted surveys is discussed. Based on the results of this survey and the data of laboratory animal and in vitro studies, an explanatory model for the etiology of PLC is proposed, taking into consideration the role of nutrition in the etiology of this disease.

Aflatoxins↗
PubMed1990

Geographic association of Helicobacter pylori antibody prevalence and gastric cancer mortality in rural China.

To examine the geographic association between Helicobacter pylori infection and gastric cancer, we have assessed the prevalence of IgG antibodies to H. pylori in plasma samples taken in 1983 from 1882 men, aged 35-64 years, in 46 rural counties of the People's Republic of China. The gastric cancer mortality rates in these countries in 1973-75 varied from 3 per 1,000 (cumulative rate, 0-64 years) to 69 per 1,000, while the proportions of the population positive for H. pylori antibodies (based on an average of about 41 men per county) varied from 28% to 96%. After correction for the limited number of blood samples per county, the estimated correlation between H. pylori antibody prevalence and gastric cancer mortality was 40% (p = 0.02). No other type of cancer showed a significant association with H. pylori.

Adult↗
PubMed1990

Effects of carotenoids on aflatoxin B1-induced mutagenesis in S. typhimurium TA 100 and TA 98.

The effects of beta-carotene, canthaxanthin, and extracts of tomato paste (containing lycopene) and orange juice (containing cryptoxanthin) on aflatoxin B1 (AFB1)-induced mutagenesis in S. typhimurium TA 100 and TA 98 were investigated. Inhibition of mutagenesis was studied during and following completion of AFB1 metabolism (i.e., after the addition of menadione), thereby permitting separate examination of the metabolic activation and phenotypic expression phases. Each experimental carotenoid, except lycopene, inhibited AFB1-induced mutagenesis in both tester strains. Cryptoxanthin was the most potent inhibitor, being at least an order of magnitude more potent than the other carotenoids. Inhibition by beta-carotene and canthaxanthin was more prominent during the activation phase, whereas cryptoxanthin was more effective during the subsequent phenotypic expression phase. These inhibitory effects were not dependent on conversion to retinol.

Aflatoxins↗
PubMed1990

Questioning riboflavin recommendations on the basis of a survey in China.

Riboflavin status was surveyed in adults aged 35-64 y in 65 counties (two communes per county) in the People's Republic of China by erythrocyte glutathione reductase activity coefficients (EGRACs), by urinary excretion of riboflavin 4 h after the oral administration of 5 mg riboflavin (one commune per county), and by direct measurement of food intake over a 3-d period (one commune per county). EGRAC data were highly correlated between sexes (p less than 0.001) and between neighboring communes within the same county (p less than 0.001) and with riboflavin intake (p less than 0.001). The urinary-riboflavin-load test data were not correlated either with EGRAC or with riboflavin intake. Approximately 90% of the survey subjects were found to be deficient by Western and Chinese reference standards and allowances. Upon reconsideration of the Western experimental data originally used to establish these recommendations, it is suggested that riboflavin allowances are set too high both in China and in Western countries.

Adult↗
PubMed1990

Urinary riboflavin excretion after a load test in rural China as a measure of possible riboflavin deficiency.

Urinary excretion of riboflavin was measured in 3318 adults 4 h after an oral dose of riboflavin. Male and female subjects aged 35-64 years were selected from 65 mostly rural counties located in 24 provinces of China. Counties were selected to represent a range of seven of the most prevalent cancer mortality rates in China and within counties households were selected at random. Urinary riboflavin excretion levels after a load test, erythrocyte glutathione reductase activity coefficients (EGR-AC), dietary riboflavin intakes, and a large number of other biochemical, dietary, and environmental parameters were measured. Mean dietary intake of riboflavin was 75 per cent of the Chinese recommended dietary allowances (CRDA). Mean meat intake per reference man was very low (26.4 +/- 23.7 g/d) in comparison to Western standards and milk was not consumed at all in most counties. Mean EGR activity coefficients measured on 'blood pools' for both males (1.47 +/- 0.14) and females (1.48 +/- 0.16) indicated that more than two-thirds of the population surveyed was in the medium or high risk category of riboflavin deficiency. Using current reference standards of less than 1.4 mg for 4-h urinary excretion of riboflavin after a 5 mg load, more than 70 per cent of the individuals examined exhibited low levels usually associated with high risk of riboflavin deficiency. In view of the lack of specificity for clinical indications of riboflavin deficiency and the tentative validity of the present CRDA, the interpretation of the data is problematic. We suggest that the present CRDA for this vitamin is set too high and requires critical review and possibly some revision.

Administration, Oral↗
PubMed1989

Effect of dietary protein quality on development of aflatoxin B1-induced hepatic preneoplastic lesions.

The effect of the quality of dietary protein on the post-initiation development of aflatoxin B1-initiated putatively preneoplastic foci in Fischer 344 rat liver was compared with the effect of the quantity of dietary protein. Feeding wheat gluten, a low-quality protein, during the postinitiation period (between the end of aflatoxin B1 dosing and the death of the rats) inhibited the development of gamma-glutamyltransferase-positive foci when compared with that in animals fed high-quality protein (casein) diets during the same period. Lysine supplementation of wheat gluten during the postinitiation period enhanced the gamma-glutamyltransferase-positive response to a level comparable with that of the high-quality protein. These results suggest that one can inhibit the development of foci either by decreasing the quantity of protein intake and holding the quality of the protein constant or by decreasing the quality and holding the quantity constant.

Aflatoxin B1↗
PubMed1989

Effect of dietary omega-3 and omega-6 fatty acids on development of azaserine-induced preneoplastic lesions in rat pancreas.

We examined the effect of varying the ratio of dietary omega-3 (omega 3) to omega-6 (omega 6) on the development of pancreatic preneoplastic lesions in male Wistar rats given azaserine at 14 days of age. As the ratio of dietary omega 3 to omega 6 fatty acids increased in a diet totaling 20% by weight of fat, the development of preneoplastic atypical acinar cell nodules (AACNs) at 4 months after dosing with azaserine decreased significantly. In addition, serum levels of prostaglandin thromboxane B2, prostaglandin E2, and 6-keto-prostaglandin F1 alpha decreased significantly. The fatty acid composition of the rbc membrane was also significantly influenced by the ratio of dietary omega 3 to omega 6 fatty acids. In a second experiment, we examined the effect of dietary intervention with a different type of fat (corn oil or menhaden oil) 2 months into the 4-month postdosing period on AACN development at the end of the post-dosing period. Intervention of the omega 6 fatty acid-rich diet with the omega 3 fatty acid-rich diet significantly decreased focal development. The opposite was true when intervention involved substituting the omega 3 fatty acid-rich diet with the omega 6 fatty acid-rich diet.

Animals↗