Reply:

Kurtovic, Jelica; Liu, Qing; Duan, Zhong Ping; Ha, Da Kang; Bengmark, S; Riordan, Stephen M.

doi:10.1002/hep.20550

Cited by 2 publications

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When 2.5–5 g three times daily of dietary supplementation with fermentable fibre are taken for 30 days, cirrhotic patients were associated with significantly reduced circulating levels of ammonia and faecal pH, and significantly increased circulating levels of SCFA [75]. Ammonia favours the growth of cancerous cells over healthy cells in vitro [57].…”

Section: Colonic Environment For Risk Of Colorectal Cancer and Relmentioning

confidence: 99%

Colorectal Carcinogenesis: A Cellular Response to Sustained Risk Environment

Fung

Ooi

Zucker

et al. 2013

IJMS

View full text Add to dashboard Cite

The current models for colorectal cancer (CRC) are essentially linear in nature with a sequential progression from adenoma through to carcinoma. However, these views of CRC development do not explain the full body of published knowledge and tend to discount environmental influences. This paper proposes that CRC is a cellular response to prolonged exposure to cytotoxic agents (e.g., free ammonia) as key events within a sustained high-risk colonic luminal environment. This environment is low in substrate for the colonocytes (short chain fatty acids, SCFA) and consequently of higher pH with higher levels of free ammonia and decreased mucosal oxygen supply as a result of lower visceral blood flow. All of these lead to greater and prolonged exposure of the colonic epithelium to a cytotoxic agent with diminished aerobic energy availability. Normal colonocytes faced with this unfavourable environment can transform into CRC cells for survival through epigenetic reprogramming to express genes which increase mobility to allow migration and proliferation. Recent data with high protein diets confirm that genetic damage can be increased, consistent with greater CRC risk. However, this damage can be reversed by increasing SCFA supply by feeding fermentable fibre as resistant starch or arabinoxylan. High protein, low carbohydrate diets have been shown to alter the colonic environment with lower butyrate levels and apparently greater mucosal exposure to ammonia, consistent with our hypothesis. Evidence is drawn from in vivo and in vitro genomic and biochemical studies to frame experiments to test this proposition.

show abstract

Section: Colonic Environment For Risk Of Colorectal Cancer and Relmentioning

confidence: 99%