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Effect of dietary fat on colonic protein kinase C and induction of aberrant crypt foci

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Lipids

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Abstract

A major objective of the present study was to determine whether a high-fat diet affects early events during colon carcinogenesis. Female Sprague-Dawley rats were injected with saline or azoxymethane (20 mg/kg) and fed either a normal (5% corn oil w/w) or a high (5% corn oil and 15% beef tallow w/w) fat diet. To assess the effect of a known tumor-promoting diet on the early events of neoplastic transformation, Study 1 examined the induction and growth of aberrant crypt foci (ACF) as well as of proliferative indices. The total number of ACF were similar in both groups even after 8 wk of dietary treatment; however, ACF with accelerated growth characteristics (≥4 crypts/focal lesions) were more prevalent (P≤0.05) in the colons of animals fed the high-fat diet. Metaphase arrest cells and 5′-bromo-2′-deoxyuridine labelled cells showed no appreciable response to dietary changes. To determine whether changes in colonic signal transduction pathways represent an early response to dietary modification, Study 2 evaluated the activity of protein kinase C (PKC), proliferative indices and changes in phospholipid fatty acid profiles. In comparison to the normal fat group, the colons of high-fat fed animals exhibited higher (P≤0.05) membranes and lower soluble PKC activity; however, proliferation patterns of these colons were not altered. Changes in the membrane lipid composition were minor; however, an increase in the phosphatidylcholine/phosphatidylethanolamine ratio and in 20∶4n−6 was noted. Our results demonstrate that in comparison to a normal-fat diet, a high-fat diet stimulated the growth of a population of ACF, i.e., preneoplastic lesions leading to advanced growth characteristics. In addition, a high-fat diet exerted a marked influence on total, cytosolic and membrane associated PKC activities. The findings suggest that modulation of PKC may play a critical role at the early stages of colon carcinogenesis.

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Abbreviations

AC:

aberrant crypt

ACF:

aberrant crypt foci

AOM:

azoxymethane

ATP:

adenosine triphosphate

BrdU:

5′-bromo-2′-deoxyuridine

DAG:

diacylglycerol

PBS:

phosphate buffered saline

PCNA:

proliferating cell nuclear antigen

PC:

phosphatidylcholine

PE:

phosphatidylethanolamine

PKC:

protein kinase C

PS:

phosphatidylserine

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Author information

Authors and Affiliations

  1. The Division of Chemistry, Environmental Health Centre, Health Protection Branch, K1A OC6, Ottawa, Ontario, Canada

    Prem Kumarathasan

  2. Department of Foods and Nutrition, The University of Manitoba, 190 Dysart Road, R3T 2N2, Winnipeg, Manitoba, Canada

    Lynne M. Z. Lafave & Ranjana P. Bird

Authors
  1. Lynne M. Z. Lafave
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  2. Prem Kumarathasan
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  3. Ranjana P. Bird
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Lafave, L.M.Z., Kumarathasan, P. & Bird, R.P. Effect of dietary fat on colonic protein kinase C and induction of aberrant crypt foci. Lipids 29, 693–700 (1994). https://doi.org/10.1007/BF02538913

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  • DOI: https://doi.org/10.1007/BF02538913

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