Brennan-Craddock, Wendy Elizabeth; (1990) The influence of host and dietary factors on mutagen metabolism in mice. Doctoral thesis (Ph.D), UCL (University College London).

Text The_influence_of_host_and_diet.pdf Download (13MB)

Abstract

The effects of quantitative and/or qualitative changes to dietary fat and protein on the genotoxicity of dietary carcinogens were evaluated in female BALB/c mice using in vivo and in vitro bacterial mutation assays. An increase in dietary fat content (from 1% to 20%) increased the in vitro activation of MelQ (2-amino-3,4-dimethylimidazo[4,5-f]quinoline) and Trp-P-2 (3-amino-l-methyl-5H-pyrido[4,3b]indole) with the extent of the increase being dependent on the type of fat used although the activation of aflatoxin Bi was unaltered. Changes in in vivo genotoxicity were also seen but these did not always reflect the in vitro results. As the protein content of the diet increased from 5% to 20% there was a decline in the in vivo mutagenicity of aflatoxin Bi (but not MelQ and Trp-P-2). Diet related changes to hepatic enzymes involved in the activation and detoxification of aflatoxin Bi do not explain the reduction in genotoxicity observed in mice fed a high protein diet. Distribution studies indicate that dietary fat and protein may influence the uptake and turnover of mutagens in the liver although fat appeared not to influence the uptake of compounds from the gastro-intestinal tract. The dietary fibre pectin significantly increased caecal nitrate reductase activity but had no apparent effect on the in vivo nitrosation of aminopyrine to the mutagen nitrosodimethylamine. Extreme changes to the gut flora (germ-free mice compared to conventional) however, did result in changes to hepatic metabolism of mutagens in vivo. As the age of mice used in genotoxicity assays increased from 2 - 24 weeks, the mutagenicity in vivo and in vitro of MelQ and Trp-P-2 decreased. Similarly, aflatoxin Bi genotoxicity was reduced in older animals in vivo but not in vitro. Changes in hepatic activation and detoxification capacity of the liver appear to explain these age dependent changes. However age had no consistent effect on gut flora metabolism. To improve the sensitivity of the host-mediated assay, various modifications to the assay were investigated and analysis of this bacterial data was assisted by electron microscopy showing bacterial distribution within the liver.

Downloads since deposit

Loading...

41Downloads

Download activity - last month

Export as XMLCSVJSON

Loading...

Download activity - last 12 months

Export as CSVXMLJSON

Loading...

Downloads by country - last 12 months

Export as JSONXMLCSV

Loading...

Archive Staff Only

View Item