How does dietary status affect carcinogenesis?

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How does dietary status affect carcinogenesis?

Cancer is a multi-factoral disease resulting from the perturbation of the normal regulatory processes of a cell. Cancer cells are generated from healthy cells by an accumulation of genetic alterations [1]. These alterations can take the form of mutations, losses, amplifications or re-arrangements in so called “oncogenes” or “tumour suppresser genes” [1]. The many potential mutations giving rise to cancer are initiated by carcinogenic substances and by certain environmental conditions [1]. Carcinogenic substances can be loosely classified as "endogenous", which may be naturally occurring, iatrogenic, environmental contaminants or life style-related or endogenous, for example reactive oxygen species which can be produced in vivo.

        The human diet consists of an array of microbial, animal and plant derived material and a link between diet and health has been recognised for many centuries [2]. The specific relationship between diet and cancer however is ill defined and uncertain and the evidence is contradictory. Dietary constituents are believed to play both a protective and causative role in the aetiology of the disease and the link between dietary factors and carcinogenesis has been relentlessly investigated by way of animal experiments. Numerous, albeit rather general epidemiological studies have also supported the notion that dietary status can influence carcinogenesis. Based on these studies it is now estimated that diet may contribute to up to 35 percent of all cancers.

Such studies form the basis of various prevention strategies, including the incorporation of potential anti-carcinogens/anti-mutagens into the diet and various dietary modifications for example an increased consumption of fruit and vegetables.

        In this project I aim to examine the evidence implementing various dietary constituents in the aetiology of cancer and their suggested mechanisms. I also aim to suggest potential dietary interventions for the prevention of cancer, reaching a conclusion as to the influence of dietary status on carcinogenesis and suggesting potential future research directions.

Dietary anticarcinogens/antimutagens.

        Laboratory studies have identified an array of anti-mutagens and anti-carcinogens (Table1.), many of which are plant derived, [2]. Anti-carcinogens/ mutagens may act via various mechanisms; by blocking the activation of the carcinogen, for example by blocking the induction of various metabolic enzymes, or by enhancing DNA repair mechanisms. Alternatively, they may “suppress” the effects of a carcinogen. Anti-mutagens can be chemicals that interfere with DNA repair or  metabolism of mutagens and mutagen scavengers, such as vitamins C and E.

Table1. Some anticarcinogens in foods.

        

Fruit and vegetables.

There is mounting evidence that a diet high in fruit and vegetables, such as citrus fruit and brassica, may offer some protection against cancers of the stomach, larynx, lung, bladder, oesophagus, cervix and colorectum [2]. More recently, studies in experimental animals have demonstrated that the feeding of specific vegetables may inhibit the development of certain chemically-induced cancers, possibly via bringing about the induction of various “phase two” metabolic enzymes, for example glutathione-S-transferases [3]. In some cases, studies have been performed directly with crude extracts of fruit and vegetables, but most involve assessing the actions of specific, isolated active compounds [4]. Many compounds have been assayed for their anti-carcinogenic effects on animals by assessing their effects on chemical, carcinogen or radiation-induced tumours [4]. Cancer protective constituents of fruit and vegetables can be divided into different groups on the basis of their chemical structure [4]. These groups include polyphenols, thiols, carotenoids, retinoids and tocopherols.

        The mechanistic basis for the anti-carcinogenic effects of fruit and vegetables is uncertain. Their anti-carcinogenic contents may act at the initiation stage of carcinogenesis by inhibiting the formation (vitamin C), uptake (cellulose) of carcinogens or their activation. Their activity may also be a result of  the prevention of initial carcinogen-induced damage and certain constituents of vegetables and fruit may serve to maximise the efficacy of DNA repair processes within the cell.

        Certain pieces of evidence suggest that the protection offered may be due to a modulation of carcinogenic metabolism and the enzyme-modulating activities of many constituents of fruit and vegetables, including flavenoids, have been examined.

Various components of fruit and vegetables, such as carotenoids are thought to possess anti-oxidant activities and thus can protect against free radicals (Figure 1.) It has been proposed that these anti-carcinogenic agents act by minimising oxidant-induced DNA or protein damage, a precursor to mutagenesis/carcinogenesis.

Figure 1. Influence of increased fruit and vegetable consumption on plasma concentrations of anti-oxidants, Week 0, plasma levels after 2 weeks of eating an average of 2.2 servings of fruit and vegetables per person per day [2].

100

30

                 

10

                 Week 0

                 

3                 Week 2

1

0.3

0.1

0.03

0.01

Beta-Carotene         Alpha-carotene           Vitamin C                Alpha-tocopherol              Retintol

   Antioxidants

β-carotene

Historically, vitamin A has be widely investigated as an anti-carcinogenic agent owing to its role in the control of cellular differentiation. During the 1980s, interest in the role of β–carotene as a potential anti-carcinogen grew [5]. β–carotene is abundant in carrots and in fact is contained in all chlorophyll-rich fruit and vegetables [4]. It is the most abundant and efficiently converted of the pro-vitamin A carotenoids, also, unlike vitamin A, serum β–carotene levels are dependent upon dietary intake. This evidence leads to a possible mechanism for β–carotene as an anti-oxidant without its conversion to vitamin A.

        Several prospective studies of carotenoid intake and carcinogenesis have been undertaken [5]. Such studies involve the collection of accurate dietary information and of blood samples. On the whole, such studies have provided further support for the role of β–carotene as an anti-carcinogenic agent. Relatively few however have actually assessed carotenoid intake by calculating the carotenoid content of certain foods.

        A number of retrospective studies of carotenoid intake and cancer, particularly lung cancer, have been conducted [5], whereby patients with a particular cancer are compared with cancer-free control subjects. These studies have provided further evidence that β–carotene does not require conversion to retinol to exert its protective effects.

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β-carotene is a proven anti-oxidant. Working in the lipid phase of the cell, carotenoids act as free radical traps, serving to quench reactive oxygen species. Based on this knowledge, a potential mechanism of action of carotenoids as anti-carcinogens may be via their anti-oxidant activity.

Vitamin C

Vitamin C or ascorbic acid has received much interest as a potential anti-carcinogenic agent and has been assessed for its anti-carcinogenic effects under a variety of experimental conditions. It is contained within a variety of fruits and vegetables, in particular citrus fruits such as oranges.

Humans and other primates ...

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