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Genotoxicity of Heat-Processed Foods: Margaretha J Agerstad, Kerstin Skog
Genotoxicity of Heat-Processed Foods: Margaretha J Agerstad, Kerstin Skog
Review
Received 4 September 2004; received in revised form 21 December 2004; accepted 10 January 2005
Available online 1 April 2005
Abstract
Gene–environment interactions include exposure to genotoxic compounds from our diet and it is no doubt, that humans are
regularly exposed to e.g. food toxicants, not least from cooked foods. This paper reviews briefly four classes of cooked food
toxicants, e.g. acrylamide, heterocyclic amines, nitrosamines and polyaromatic hydrocarbons. Many of these compounds have
been recognised for decades also as environmental pollutants. In addition cigarette smokers and some occupational workers are
exposed to them. Their occurrence, formation, metabolic activation, genotoxicity and human cancer risk are briefly presented
along with figures on estimated exposure. Several lines of evidence indicate that cooking conditions and dietary habits can
contribute to human cancer risk through the ingestion of genotoxic compounds from heat-processed foods. Such compounds
cause different types of DNA damage: nucleotide alterations and gross chromosomal aberrations. Most genotoxic compounds
begin their action at the DNA level by forming carcinogen–DNA adducts, which result from the covalent binding of a carcinogen
or part of a carcinogen to a nucleotide. The genotoxic and carcinogenic potential of these cooked food toxicants have been
evaluated regularly by the International Agency for Research on Cancer (IARC), which has come to the conclusion that several
of these food-borne toxicants present in cooked foods are possibly (2A) or probably (2B) carcinogenic to humans, based on
both high-dose, long-term animal studies and in vitro and in vivo genotoxicity tests. Yet, there is insufficient scientific evidence
that these genotoxic compounds really cause human cancer, and no limits have been set for their presence in cooked foods.
However, the competent authorities in most Western countries recommend minimising their occurrence, therefore this aspect is
also included in this review.
© 2005 Elsevier B.V. All rights reserved.
Keywords: Acrylamide; Heterocyclic amines; Polyaromatic hydrocarbons; Nitrosamines; Formation; Occurrence; Exposure; Cancer risk;
Minimising strategies
0027-5107/$ – see front matter © 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.mrfmmm.2005.01.030
M. Jägerstad, K. Skog / Mutation Research 574 (2005) 156–172 157
Contents
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
2. Acrylamide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
2.1. Genotoxicity and metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
2.2. Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
2.3. Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
3. Heterocyclic amines (HCAs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160
3.1. Genotoxicity and metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
3.2. Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
3.3. Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
4. N-nitroso compounds (NOCs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
4.1. Genotoxicity and metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163
4.2. Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
4.3. Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164
5. Polycyclic aromatic hydrocarbons (PAHs) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
5.1. Genotoxicity and metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
5.2. Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
5.3. Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
6. Minimising strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167
7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
formation, metabolic activation, genotoxicity and hu- that has been treated with polyacrylamide in a refin-
man cancer risk along with figures on estimated daily ing process [17]. A maximum tolerable level of 0.1 g
intakes and ways to minimising the occurrence of these acrylamide per liter water has recently been established
heat-induced food toxicants. For more details, see some within the European Union [18]. In addition, tobacco
reviews given in the reference list [7–15]. smokers are highly exposed to acrylamide. Bergmark
[19] determined the level of acrylamide adducts in
blood samples from smokers and non-smokers work-
2. Acrylamide ing with polyacrylamide gels for electrophoresis. The
levels of haemoglobin adducts in smokers were twice
Acrylamide has been manufactured in big scale the level in the non-smoking laboratory personnel.
since the 1950s mainly to produce water-soluble poly- In the same survey, it was concluded that also non-
acrylamides used as flocculents for clarifying drinking smokers had elevated levels of acrylamide adducts.
water, for treating municipal and industrial waste wa- The high background of acrylamide adducts in the non-
ters and as flow control agents in oil-well operations. smoking control group was unexpected and the authors
Other major uses of acrylamide are in soil stabilisation, offered no explanation. A part of the explanation came
in grout for repairing sewers and in acrylamide gels 3 years later when Tareke et al. [20] found increased
used in biotechnology laboratories. Chemically, acry- haemoglobin adduct levels in rats fed with fried ani-
lamide is a water-soluble low-molecular compound mal standard diet. During the same period, also Peres
(MW 79.01) built up of a reactive ethylenic double [21] measured surprisingly high levels of acrylamide
bound linked with a carboxamide group (Fig. 1) [16]. in coffee. These early observations in the year 2000
The general opinion has been that the main hu- were largely ignored. However, 2 years later, Tareke et
man exposure to acrylamide is of occupational origin al. [6] showed that the high background level of acry-
in the industrial production of polyacrylamide, while lamide in humans was due to compounds in the diet by
the general public may be exposed by drinking water demonstrating relatively high levels of acrylamide in
IARC [16] makes an overall evaluation that acry- Based on all analyses of acrylamide in foods that
lamide is probably carcinogenic to humans (Group 2A) already have been published, WHO [26] estimated an
based on the following overall evaluation: “There is intake of acrylamide to be in the range of 0.3–0.8 g/kg
inadequate evidence in humans for the carcinogenic- bodyweight per day for an adult corresponding to
ity of acrylamide. There is sufficient evidence in ex- 21–56 g/day for a person weighing 70 kg. It is im-
perimental animals for the carcinogenicity of acry- portant to take into account that there may also be
lamide. In making the overall evaluation, the Work- certain groups of people with much higher intake
ing Group took into consideration the following sup- of acrylamide. A higher estimated daily exposure,
porting evidences: (i) acrylamide and its metabo- about 100 g per person including acrylamide origi-
lite glycidamide form covalent adducts with DNA in nating from cosmetics and tobacco based on average
mice and rats; (ii) acrylamide and glycidamide form haemoglobin adducts level in the Swedish population,
covalent adducts with haemoglobin in exposed hu- was also reported [6].
mans and rats; (iii) acrylamide induces gene muta-
tions and chromosomal aberrations in germ cells of
mice and chromosomal aberrations in germ cells of 3. Heterocyclic amines (HCAs)
rats and forms covalent adducts with protamines in
germ cells of mice in vivo; (iv) acrylamide induces Research leading to the discovery of a series of mu-
chromosomal aberrations in somatic cells of rodents tagenic and carcinogenic heterocyclic amines (HCAs)
in vivo; (v) acrylamide induces gene mutations and was inspired by the idea that smoke produced during
chromosomal aberrations in cultured cells in vitro; (vi) cooking of food, especially meat or fish, might be car-
acrylamide induces cell transformation in mouse cell cinogenic [4,5]. More than 20 derivatives of HCAs,
lines”. actually produced by cooking or heating of meat or
When calculating cancer risk for humans, reliable fish, have now been isolated and their structures deter-
data from epidemiological studies are of course better mined, most being previously unregistered compounds
than an extrapolation from animal studies using high [14,15]. Generally, they all consist of two or three
doses of acrylamide. Due to the fact that acrylamide is rings with an exocyclic amino group attached to one
produced in many different types of foodstuffs, it may of the rings. Depending on their chemical structures
be difficult to find sufficiently large differences in ex- they can be divided into the following sub-groups:
posure between the studied groups, which is a prereq- amino-carbolines (e.g. AAC), imidazo-quinolines(e.g.
uisite in epidemiological studies. So far a few epidemi- IQ) and imidazoquinoxalines (e.g. MeIQx) and imi-
ological studies on cancer risk with dietary acrylamide dazopyridines (e.g. PhIP). The chemical structure and
intake have been published. Mucci et al. [23] found a trivial names of some HCAs are shown in Fig. 1. For
lack of an excess risk of cancer of the large bowel, blad- full names, see the list of abbreviations.
der or kidney in Swedish consumers of foods contain- The imidazo-quinolines, imidazoquinoxalines and
ing moderate (30–299 g) or high (300–1200 g/kg) imidazopyridines may be formed from creatine or crea-
levels of acrylamide. Pelucchi et al. [24] and Dybing tinine, certain free amino acids and sugars via the Mail-
and Sanner [25] reported similar results. Although the lard reaction [27]. These three groups of precursors are
absence of an association in a population-based study all present in uncooked meat and fish muscle, where
seems reassuring, there is a need to extend the epi- free amino acids and sugars are supplied from muscle
demiological evaluation to other cancer sites (e.g. lung, protein and glycogen, respectively, whereas creatine is
pancreas, testis) in view of the fact that smoking sig- an energy metabolite only present in significant levels
nificantly increases the body burden of acrylamide. in muscle cells. Following cooking at high tempera-
Moreover, epidemiological studies have so far not been tures, HCAs are produced in ng/g. In general pan-frying
designed to detect any estimated stochastic (random) and grilling produce high yield of HCAs at cooking
small increase in the incidence of cancer related to temperatures from 200 ◦ C and above, boiling yields
acrylamide. little or no HCAs, and deep-fat frying, roasting, and
M. Jägerstad, K. Skog / Mutation Research 574 (2005) 156–172 161
Table 5
Daily intake of nitrosodimethylamine (NDMA) in different countries (from [12])
Country NDMA intake (g/day) Major NDMA source
UKa 0.53 Cured meats (81%)
UK 0.6 Beer, cured meats
The Netherlands 0.38 Beer (71%)
The Netherlandsb 0.10 Not evaluated
FRG (1979/1980) 1.10 (men) Beer (65%)
FRG (1979/1980) 0.57 (women) Cured meats (10%)
FRG (1981) 0.53 (men) Beer (40%)
FRG (1981) 0.35 (women) Cured meats (18%)
FRG (1989/1990) 0.28 (men) Beer (31%)
FRG (1989/1990) 0.17 (women) Cured meats (36%)
Japan 1.8 Dried fish (91%)
Japan 0.5 Fish products (68%), beer (30%)
Sweden 0.12 Meat products (61%), beer (32%)
Finlandc 0.08 Smoked fish (75%)
China No data Marine foods
Italy No data Cured meats
USSR No data Meat and fish products
a Beer not included in the survey.
b Determined by 24 h duplicate diet analysis.
c Based on limited data.
M. Jägerstad, K. Skog / Mutation Research 574 (2005) 156–172 165
lung cancer can be induced. Eleven PAH compounds There is however no conclusive evidence concern-
have been classified as carcinogenic to laboratory ani- ing a possible relationship between ingestion of PAH-
mals [2,3]. However, The Committee on Diet, Nutrition contaminated food and human cancer. A few studies
and Cancer, appointed by the National Research Coun- (for reference, see [109]) have suggested a link be-
cil of the USA, stated in their report that of the PAHs oc- tween an increased incidence of stomach cancer and
curring in the average American diet only three, namely frequent consumption of smoked food. However, as
B[a]P, benz[a]anthracene, and dibenz[a,h]anthracene, smoked food may contain other potentially carcino-
have been found to be carcinogenic in animals follow- genic substances, such as nitrite and nitrosamines, the
ing oral administration. observed effects cannot definitively be related to PAHs.
These three food PAHs have been considered prob- Animal and human studies suggest that dietary PAH
ably (Group 2A) carcinogenic to humans on the basis is distributed to other organs besides the locally ex-
of data obtained from animal experiments and in vitro posed tissues, so it is plausible to consider that dietary
test systems. In addition, experimental data indicate PAH might contribute to lung or breast cancer risk,
that other such compounds may possibly (Group 2B) for example. Although the dietary contribution of PAH
be carcinogenic to humans [1,2]. The effects of human to the total body burden may be sizeable, the ubiq-
PAH exposure are measured mostly in relationship to uitous presence of PAH in the environment and the
tobacco smoking and the work place, and data indicate presence of other carcinogens in the same foods makes
that the target organs for PAH compounds are the lung, the interpretation of epidemiological studies of can-
oropharynx, breast and genitourinary and gastrointesti- cer risk due to dietary PAH difficult. It may be pos-
nal tracts. However, dietary PAH exposure and cancer sible to distinguish PAH exposure in diet from smok-
risk has received little attention. A fairly consistent as- ing by measuring biomarkers specific to each, e.g. si-
sociation between grilled (broiled), but not fried, fish multaneous measurement of 1-hydroxypyrene to eval-
and meat and stomach cancer suggests that dietary ex- uate total PAH intake and 4-(methylnitrosoamino)-1-
posure to PAHs may be involved in human gastric car- (3-pyridyl)-1-butanol to evaluate the contribution due
cinogenesis. In humans there is also some evidence to smoking. In addition, dietary PAH is invariably a
for association of dietary PAH exposure with colon complex mixture of compounds with hard-to-predict
cancer. metabolic and carcinogenic consequences. Corrobora-
Fig. 2. Estimated contribution (in %) of various food groups in an average Swedish diet to the total dietary intake of nine PAHs (fluoran-
thene, pyrene, benz[a]anthracene, chrysene/triphenylene, benzo[b]fluoranthene, benzo[j]fluoranthene/benzo[k]fluoranthene, benzo[e]pyrene,
benzo[a]pyrene, and indeno[1,2,3-cd]pyrene) (Larsson [105]), permission to be applied for).
M. Jägerstad, K. Skog / Mutation Research 574 (2005) 156–172 167
tive data that indicate that PAH exposure from diet is their presence in cooked foods. However, the compe-
important are the findings that the intake of charcoal- tent authorities in most Western countries recommend
broiled meat is more correlated to blood PAH DNA minimising their occurrence for safety reasons.
adducts than smoking [108]. Friedman [7] suggests several actions to reduce
acrylamide content of food in his comprehensive re-
5.3. Exposure view, e.g. better understanding of kinetics and cook-
ing/processing conditions that reduce the acrylamide
The dietary intake of PAHs in Europe, USA and formation. Moreover different ways to reduce the pres-
Japan has been estimated to be around 1 mg per per- ence of the acrylamide precursor asparagin and sugars
son per year. Most data are for B[a]P, with values in in food by careful selecting of raw materials and studies
the range 0.01–0.61 mg per person per year. Thus, a of breeding and/or suppressing genes that encode en-
daily average intake of 2–3 g PAHs per person seems zymes which govern the biosynthesis of asparagine in
reasonable, of which B[a]P constitutes 0.5–5%. The av- plant foods. Use of chemical and biochemical tools, e.g.
erage daily intake of PAHs compares to an exposure of changes in pH, use of hydrolysing enzymes from yeast
2–5 g PAHs per pack of cigarettes in a regular smoker. or lactic acid producing bacteria during bread making,
Fig. 2 illustrates the estimated contribution of various addition of inhibitors and modifiers, and changes in
food groups in an average Swedish diet to the intake of recipe of foods are other options.
nine commonly reported PAHs in food. The major part Recently, Persson et al. investigated ways of modi-
of the PAHs intake is due to contamination through air fying cooking practise to reduce the formation of HCAs
pollution and only about 25–30% of the PAHs origi- [112,113]. Various factors that influence the forma-
nate from cooking, mainly grilled or smoked foods (for tion of HCAs during cooking of chicken breasts and
reference, see [110]). beef burgers were investigated. The factors studied in-
cluded cooking method, time, temperature, heat trans-
fer, weight loss during cooking, the chemical compo-
6. Minimising strategies sition of beef burgers and antioxidants. The conditions
for the cooking experiments were similar to those used
Following a number of evaluations, the IARC has in normal domestic restaurants and industrial cooking.
come to the conclusion that several of these food-borne The analysis of HCAs was focused mainly on MeIQx
toxicants present in cooked foods are possibly (2A) or and PhIP and a few more. The HCA concentrations
probably (2B) carcinogenic to humans, based on both ranged from undetectable amounts to 30 ng/g cooked
high-dose, long-term animal studies and in vitro and meat. Cooking temperature was shown to be an impor-
in vivo genotoxicity tests. Generally, animal experi- tant factor, especially during frying, since large concen-
ments concerning genotoxic effects are conducted in tration of HCAs can be formed at high temperatures.
high doses on rodents, which are exposed during their Avoiding over-cooking of meat seems thus to be an im-
whole life span, 1–3 years. The test-doses used in an- portant way to decrease the content of HCAs. Reducing
imal experiments are based on synthetic compounds the weight loss during cooking may be means of de-
of authentic single food processing toxicants amount- creasing the formation of HCAs, and this correlation is
ing to 0.1–2% of the feed. These amounts exceed the probably due to the transport of water-soluble precur-
daily human intakes by a factor of 1000–10 000. Usu- sors to the meat surface. This transport can be lowered
ally humans are exposed to food processing toxicants by the addition of water-holding ingredients, such as
in g-levels on daily basis during a lifespan of around common salt or potato starch. Addition of carbohy-
70–80 years. Based on studies of biomarkers or sur- drates may also affect the formation of HCAs chem-
rogate markers, e.g. adducts, specific mutations and ically. Frying in oil containing antioxidants may also
urinary excretion, a growing number of human stud- provide a way of reducing the amount of HCAs formed,
ies indicate that food processing toxicants are bioavail- although the amounts of antioxidants and the effect
able in a dose-dependent way [40–48]. Yet, there is of storage must be taken into consideration. A kinetic
insufficient scientific evidence that these toxicants re- model was used to describe the formation of HCAs and
ally cause human cancer, and no limits have been set for this can be further developed to predict the formation of
168 M. Jägerstad, K. Skog / Mutation Research 574 (2005) 156–172
HCAs [27]. The results from this research can be used melted fat from dripping onto the heat source, reduces
to design cooking equipment and processes and to form the PAHs contamination significantly. In some coun-
a basis for guidelines to consumers, restaurants and in- tries, legislative limits have been set for PAHs in certain
dustry, on how to obtain a product with good sensoric foods, with the aim of minimising the intake of PAHs.
properties and minimised contents of HCAs. In Germany, Poland and Austria a limit of 1 g/kg is
The natural variation of the concentrations of HCA currently imposed for B[a]P in smoked meat products.
precursors in pig meat has been investigated [114].
While production system, sex and feeding regime
showed little effect on precursor concentrations in pig 7. Conclusions
meats, a common genotype (RN− -allele carriers) was
characterised by resulting in high glycogen concentra- Several lines of evidence indicate that cooking con-
tions. The high glycogen content in carriers of the RN ditions and dietary habits can contribute to human can-
allele led to a browner crust and considerably lower lev- cer risk through the ingestion of food mutagens. This
els of HCAs in fried meat compared to that of normal is of concern for the general public and also for the
genotype [115]. food industry and national authorities. Food mutagens
Except minimising the intake of HCAs there are also cause different types of DNA damage: nucleotide alter-
an emerging interest among many scientists to inves- ations and gross chromosomal aberrations. Most mu-
tigate the numerous environmental chemicals found in tagens begin their action at the DNA level by forming
food or the atmosphere which can impact the exposure, carcinogen–DNA adducts, which result from the co-
metabolism and cell proliferation response of hetero- valent binding of a carcinogen or part of a carcinogen
cyclic amines, e.g. it may be wise to include food items to a nucleotide. However, the effect of food mutagens
rich in compounds protecting bioactivation of HCAs, in carcinogenesis can be modified by heritable traits,
e.g. soy-isoflavones [15]. namely, low-penetrant genes that affect mutagen expo-
During recent years, the levels of N-nitroso com- sure of DNA through metabolic activation and detoxi-
pounds in the human diet have decreased significantly. fication or cellular responses to DNA damage through
This is due to reductions in the levels of nitrates and ni- DNA repair mechanisms or cell death [108].
trites added to foods, and the simultaneous addition of This article has focused on the most commonly
ascorbic acid, which inhibits the formation of N-nitroso studied food toxicants present in cooked foods. The
compounds in cured meat products. Recommendations fact is however, that new process-induced genotoxic
have been made to fry bacon with caution, not to use compounds are continuously reported. One large group
lids and not to consume the frying fat rendered out of of cooked food mutagens not reviewed in the present
the bacon, i.e. the pan residue. Soaking bacon in water paper includes oxidised sterols arising from oxida-
before frying, as well as microwave cooking instead of tion of cholesterol and phytosterols during processing
using a griddle or a frying pan, significantly lowers the and storage of foods. For cholesterol and phytosterols
NPYR levels [79]. more than 100 different oxidation products are reported
For any cooking involving wood fires, the type of among which different epoxides are frequently seen.
wood used can also be important. For example, hard- While cholesteroloxides have been found to be mu-
wood such as oak and hickory, burn cleanly, whereas tagenic, cytotoxic or atherogenic, the oxidation prod-
some woods such as mesquite, but also cones generate ucts from phytosterols have been studied to a very lit-
copious quantities of PAHs. Ways of minimising ex- tle extent. Yet, preliminary reports show many differ-
posure to PAHs from cooked foods include preventing ent foods, in particular French fries, to contain as high
the smoke from the combustion of wood or fossil fuels concentrations of oxidised sterols as acrylamides, for
to come into direct contact with the food, when barbe- reference, see [116].
cuing or smoking foods, unless the smoke is purified Traditionally, scientists are specialised on only one
with regard to PAHs. Cooking over a log fire in direct aspect of one group of food mutagens at a time. There is
contact with the flames should be avoided. It is impor- now an urgent need of a new approach to investigate the
tant to wait until the log fire has turned into embers. In impact of known food mutagens using more integrated
addition, the use of special grills, designed to prevent and sophisticated animal and human models based on
M. Jägerstad, K. Skog / Mutation Research 574 (2005) 156–172 169
more realistic exposure levels. The rapid development [13] N.J. Gooderham, S. Murray, A.M. Lynch, M. Yadollahi-
of more specific biomarkers or surrogate biomarkers is Farsani, K. Zhao, K. Rich, A.R. Boobis, D.S. Davies, As-
sessing human risk to heterocyclic amines, Mutat. Res. 376
encouraging and promising for future risk assessment
(1997) 53–60.
studies and should enable researchers from different [14] T. Sugimura, K. Wakabayashi, H. Nakagama, M. Nagao,
disciplines to work together. Heterocyclic amines: mutagens/carcinogens produced during
cooking of meat and fish, Cancer Sci. 95 (2004) 290–299.
[15] J.S. Felton, M.G. Knize, L.M. Bennett, M.A. Malfatti, M.E.
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