Welcome to the website of the AMBIPAH
project.
AMBIPAH is a project funded under the 5th Framework
Programme of the European Union (Quality of Life and Management of Living
Resources). Its aim is to investigate the existence of biological interactions
between individual polycyclic aromatic hydrocarbons (PAHs) present in the the
ambient air mixture and their possible impact on mixture carcinogenic potency.
Background
Polycyclic aromatic hydrocarbons (PAHs) make up a group of carcinogenic
chemicals found widely in the environment, especially in the polluted urban air.
Current efforts to estimate their contribution to cancer risks of humans exposed
to air pollution involve a number of simplifying assumptions and thus entail a
high degree of uncertainty which hinders the derivation of exposure limits. One
of these assumptions is that the carcinogenic potency of PAH mixtures is equal
to the sum of the individual PAH components, something which ignores the
possibility that mixture potency may be modified by biological interactions
between mixture components. The main objective of this project is to examine the
validity of this assumption and to assess the degree to which such may lead to
deviations from additivity in the cancer risk of PAHs present in the ambient
air.
Scientific approach
Six PAHs
of found in ambient air (benzo[a]pyrene, dibenzo[a,h]anthracene, fluoranthene,
dibenzo[a,l]pyrene, benzo[b]-fluoranthene
and 1-methyl-phenanthrene) are being
investigated in different in
vitro and in vivo systems with regard to their ability to cause changes related
to tumour initiation and tumour promotion. Based on the outcome of such studies,
the ability of
mixtures of
selected
PAHs to induce such changes
is
also be examined and compared with
that expected from the sum of the individual components. The
project involves the following
types of studies:
In vitro studies.
Precision-cut slices of rat lung and liver, as well as microsome preparations,
are
employed to examine the effects of
test agents on CYP1A1 expression, binding to the aromatic hydrocarbon receptor,
global gene expression profiles, PAH metabolism and DNA damage. Limited
analogous studies are
also being
performed using human tissue slices. Additional in vitro studies
are
conducted to obtain quantitative
estimates of mutagenic potencies of individual PAHs, in order to calculate their
rad-equivalence. The above effects are
being examined for individual
PAHs as well as for mixtures selected on the basis of the results obtained. The
interactions between mixture components and their impact on mixture potency
is
examined.
Short-term animal studies. The in vivo ability of the text chemicals to cause similar effects as above, as well as to give rise to
serum albumin adducts and somatic gene mutations is examined in wild-type or λlacZ transgenic mice treated with single
or multiple doses. The impact of interactions between different PAHs acting in mixtures, especially at low doses, is also under
Animal bioassays.
Based on the outcome of the short-term in vivo and in vitro studies described
above, carcinogenic potency a two
of the test PAHs, acting
individually or as a mixture, will be examined directly in carcinogenesis
assay using newborne CD1 mice.
The
results of the above studies will be assessed as regards their significance for
the definition of improved air quality standards and
monitoring strategies to assure higher protection of public health.