217
Agency for Research on Cancer to be possibly carcinogenic (group 2B) for humans
(IARC 1993), meaning that steady toxin exposure must be considered as a cause for
serious concern. With respect to chemical carcinogens, not only dosage but, more
importantly, the time-dosage profile (c 3 t product) has to be considered as relevant
for tumor development. In this respect the ubiquitous presence of OTA is a subject
of a toxicological debate presently.
Liver elimination of OTA is maintained by protein carriers that shuffle the toxin
from its protein-bound form in blood into the hepatocyte and subsequently secrete
the toxin into bile. The uptake carrier has been identified (Kontaxi et al. 1996), but
less is known about the mechanism involved in the release into bile. A carrier system is also involved in the uptake of OTA by proximal tubule cells, which secrete
the toxin into urine (Tsuda et al. 1999). Such systems are biological entrance gates
that determine the elimination toxicokinetics of OTA and therefore have a major
impact on half-life times and selective organ exposure (Petzinger and
Weidenbach 2002).
12.11 Fumonisins
Fumonisins (Fig. 12.3) are synthesized by Fusarium verticillioides and Fusarium
proliferatum fungi, under favorable high-temperature and humid climates, and they
are frequently found in maize and other cereal grains. In humans, fumonisins are
associated with neural tube defects, as well as hepatic and esophageal cancer.
Among the various types, fumonisin B1 (FB1) is the most commonly found and
predominant cancer promoter for humans. FB1 contamination in maize and maizebased products has been found in several countries, and it is estimated that more
than half of the maize products around the world are contaminated. The FAO/WHO
reported in 2011 that 63% of maize samples and 80% of the maize-based product
samples were contaminated with FB1. Rice contaminated with FB1 in Japan, Korea,
and Canada has also been described. In addition to maize and rice, FB1 can contaminate sorghum, wheat, barley, soybeans, black tea, and even milk.
Initially described and characterized in 1988, these substances are produced by
several species of the genus Fusarium, especially by Fusarium verticillioides (previously classified as Fusarium moniliforme), Fusarium proliferatum and Fusarium
nygamai, besides Alternaria alternata f.sp. lycopersici. Other species, such as
Fusarium anthophilum, Fusarium dlamini, Fusarium napiforme, Fusarium subglutinans, Fusarium polyphialidicum, and Fusarium oxysporum, have also been
included in the group of producers of these mycotoxins. Fumonisins constitute a
group which include, to date, 16 substances referred to as B1 (FB1, FB2, FB3, and
FB4), A1, A2, A3, AK1, C1, C3, C4, P1, P2, P3, PH1a, and PH1b. The presence of
fumonisins in corn grains has been associated with cases of esophageal cancer in
inhabitants of the region of Transkei in southern Africa, in China, and in northeastern Italy. Fumonisins are also responsible for the leukoencephalomalacia in equine
species and rabbits; pulmonary edema and hydrothorax in pigs; and hepatotoxic,
carcinogenic, and apoptosis (programmed cell death) effects in the liver of rats.
12 Fungal Mycotoxins
Agency for Research on Cancer to be possibly carcinogenic (group 2B) for humans
(IARC 1993), meaning that steady toxin exposure must be considered as a cause for
serious concern. With respect to chemical carcinogens, not only dosage but, more
importantly, the time-dosage profile (c 3 t product) has to be considered as relevant
for tumor development. In this respect the ubiquitous presence of OTA is a subject
of a toxicological debate presently.
Liver elimination of OTA is maintained by protein carriers that shuffle the toxin
from its protein-bound form in blood into the hepatocyte and subsequently secrete
the toxin into bile. The uptake carrier has been identified (Kontaxi et al. 1996), but
less is known about the mechanism involved in the release into bile. A carrier system is also involved in the uptake of OTA by proximal tubule cells, which secrete
the toxin into urine (Tsuda et al. 1999). Such systems are biological entrance gates
that determine the elimination toxicokinetics of OTA and therefore have a major
impact on half-life times and selective organ exposure (Petzinger and
Weidenbach 2002).
12.11 Fumonisins
Fumonisins (Fig. 12.3) are synthesized by Fusarium verticillioides and Fusarium
proliferatum fungi, under favorable high-temperature and humid climates, and they
are frequently found in maize and other cereal grains. In humans, fumonisins are
associated with neural tube defects, as well as hepatic and esophageal cancer.
Among the various types, fumonisin B1 (FB1) is the most commonly found and
predominant cancer promoter for humans. FB1 contamination in maize and maizebased products has been found in several countries, and it is estimated that more
than half of the maize products around the world are contaminated. The FAO/WHO
reported in 2011 that 63% of maize samples and 80% of the maize-based product
samples were contaminated with FB1. Rice contaminated with FB1 in Japan, Korea,
and Canada has also been described. In addition to maize and rice, FB1 can contaminate sorghum, wheat, barley, soybeans, black tea, and even milk.
Initially described and characterized in 1988, these substances are produced by
several species of the genus Fusarium, especially by Fusarium verticillioides (previously classified as Fusarium moniliforme), Fusarium proliferatum and Fusarium
nygamai, besides Alternaria alternata f.sp. lycopersici. Other species, such as
Fusarium anthophilum, Fusarium dlamini, Fusarium napiforme, Fusarium subglutinans, Fusarium polyphialidicum, and Fusarium oxysporum, have also been
included in the group of producers of these mycotoxins. Fumonisins constitute a
group which include, to date, 16 substances referred to as B1 (FB1, FB2, FB3, and
FB4), A1, A2, A3, AK1, C1, C3, C4, P1, P2, P3, PH1a, and PH1b. The presence of
fumonisins in corn grains has been associated with cases of esophageal cancer in
inhabitants of the region of Transkei in southern Africa, in China, and in northeastern Italy. Fumonisins are also responsible for the leukoencephalomalacia in equine
species and rabbits; pulmonary edema and hydrothorax in pigs; and hepatotoxic,
carcinogenic, and apoptosis (programmed cell death) effects in the liver of rats.
12 Fungal Mycotoxins