Dietary and other Modulators of Carcinogenesis

Nutritional or dietary status and interactions between carcinogens and nutrient absorption, storage or metabolism influence carcinogenesis in many experimental animal models and probably in people. Use of dose-response data to indicate a threshold exposure for carcinogenesis must include consideration of dietary and nutritional factors that may alter the dose response. Two models in rats in which there is clear evidence of dietary or nutritional modulation of chemical carcinogenesis are mammary tumors induced by 7, 12-dimethylbenzanthracene (DMBA) or N-nitrosomethyl-urea (NMU) and hepatocarcinomas induced by many compounds. Mammary tumorigenesis is increased by increasing dietary content of some, but not all, fats. The time in tumor development at which fats act varies. Their mechanisms of action are not known but appear to include effects on the hormonal mileu and possibly mammary gland cell turnover and response to hormones. Hepatocarcinogenesis by chemicals is increased by dietary deficiency of the lipotropes methionine, choline and folate, possibly through alteration of carcinogen metabolism and increased hepatocyte DNA synthesis. The same deficiency induces cirrhosis. In humans, cirrhosis induced by alcoholism, viral hepatitis or unknown factors increases the risk for hepatocarcinoma. Alcohol-induced folate or other deficiency can be a contributory factor in the alcoholics. Infection with hepatitis B virus is increased in alcoholics and in patients with hepatocarcinoma and may be an initiating or modulating factor for tumors.

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Weighted mixed-effects dose–response models for tables of correlated contrasts

The Stata Journal Promoting communications on statistics and Stata ◽

10.1177/1536867x211025798 ◽

2021 ◽

Vol 21 (2) ◽

pp. 320-347

Author(s):

Nicola Orsini

Keyword(s):

Dose Response ◽

Response Pattern ◽

Mixed Effects ◽

Data Generation ◽

Measures Of Association ◽

Response Models ◽

Response Data ◽

Hazard Ratios ◽

Health Related ◽

Generation Mechanisms

Recognizing a dose–response pattern based on heterogeneous tables of contrasts is hard. Specification of a statistical model that can consider the possible dose–response data-generating mechanism, including its variation across studies, is crucial for statistical inference. The aim of this article is to increase the understanding of mixed-effects dose–response models suitable for tables of correlated estimates. One can use the command drmeta with additive (mean difference) and multiplicative (odds ratios, hazard ratios) measures of association. The postestimation command drmeta_graph greatly facilitates the visualization of predicted average and study-specific dose–response relationships. I illustrate applications of the drmeta command with regression splines in experimental and observational data based on nonlinear and random-effects data-generation mechanisms that can be encountered in health-related sciences.

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Archiving of Food Samples from Restaurants and Caterers—Quantitative Profiling of Outbreaks of Foodborne Salmonellosis in Japan

Journal of Food Protection ◽

10.4315/0362-028x-67.9.2024 ◽

2004 ◽

Vol 67 (9) ◽

pp. 2024-2032 ◽

Cited By ~ 10

Author(s):

FUMIKO KASUGA ◽

MASAMITSU HIROTA ◽

MASAMICHI WADA ◽

TOSHIHIKO YUNOKAWA ◽

HAJIME TOYOFUKU ◽

...

Keyword(s):

Dose Response ◽

Storage System ◽

Epidemiological Data ◽

Food Samples ◽

Food Storage ◽

Disease Rate ◽

Data Sets ◽

Response Data ◽

Quantitative Profiling

The Ministry of Health, Labor and Welfare (former MHW) of Japan issued a Directive in 1997 advising restaurants and caterers to freeze portions of both raw food and cooked dishes for at least 2 weeks. This system has been useful for determining vehicle foods at outbreaks. Enumeration of bacteria in samples of stored food provide data about pathogen concentrations in the implicated food. Data on Salmonella concentrations in vehicle foods associated with salmonellosis outbreaks were collected in Japan between 1989 and 1998. The 39 outbreaks that occurred during this period were categorized by the settings where the outbreaks took place, and epidemiological data from each outbreak were summarized. Characteristics of outbreak groups were analyzed and compared. The effect of new food-storage system on determination of bacterial concentration was evaluated. Freezing and nonfreezing conditions prior to microbial examination were compared in the dose-response relationship. Data from outbreaks in which implicated foods had been kept frozen suggested apparent correlation between the Salmonella dose ingested and the disease rate. Combined with results of epidemiological investigation, quantitative data from the ingested pathogen could provide complete dose-response data sets.

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Evaluation ofElephantopus scaberon the inhibition of chemical carcinogenesis and tumor development in mice

Pharmaceutical Biology ◽

10.3109/13880200903133845 ◽

2010 ◽

Vol 48 (3) ◽

pp. 342-348 ◽

Cited By ~ 6

Author(s):

B.S. Geetha ◽

P.G. Latha ◽

P. Remani

Keyword(s):

Tumor Development ◽

Chemical Carcinogenesis

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Telomerase activation in mouse mammary tumors: lack of detectable telomere shortening and evidence for regulation of telomerase RNA with cell proliferation.

Molecular and Cellular Biology ◽

10.1128/mcb.16.7.3765 ◽

1996 ◽

Vol 16 (7) ◽

pp. 3765-3772 ◽

Cited By ~ 112

Author(s):

D Broccoli ◽

L A Godley ◽

L A Donehower ◽

H E Varmus ◽

T de Lange

Keyword(s):

Cell Proliferation ◽

Tumor Development ◽

Mammary Tumorigenesis ◽

Mammary Tumors ◽

Mammary Glands ◽

Telomerase Activity ◽

Telomerase Rna ◽

Proliferating Cells ◽

Telomere Shortening ◽

Mouse Mammary Tumors

Activation of telomerase in human cancers is thought to be necessary to overcome the progressive loss of telomeric DNA that accompanies proliferation of normal somatic cells. According to this model, telomerase provides a growth advantage to cells in which extensive terminal sequence loss threatens viability. To test these ideas, we have examined telomere dynamics and telomerase activation during mammary tumorigenesis in mice carrying a mouse mammary tumor virus long terminal repeat-driven Wnt-1 transgene. We also analyzed Wnt-1-induced mammary tumors in mice lacking p53 function. Normal mammary glands, hyperplastic mammary glands, and mammary carcinomas all had the long telomeres (20 to 50 kb) typical of Mus musculus and did not show telomere shortening during tumor development. Nevertheless, telomerase activity and the RNA component of the enzyme were consistently upregulated in Wnt-1-induced mammary tumors compared with normal and hyperplastic tissues. The upregulation of telomerase activity and RNA also occurred during tumorigenesis in p53-deficient mice. The expression of telomerase RNA correlated strongly with histone H4 mRNA in all normal tissues and tumors, indicating that the RNA component of telomerase is regulated with cell proliferation. Telomerase activity in the tumors was elevated to a greater extent than telomerase RNA, implying that the enzymatic activity of telomerase is regulated at additional levels. Our data suggest that the mechanism of telomerase activation in mouse mammary tumors is not linked to global loss of telomere function but involves multiple regulatory events including upregulation of telomerase RNA in proliferating cells.

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