Page 590 - The Toxicology of Fishes

570 The Toxicology of Fishes

et al., 2002). This study showed that the basic husbandry practices of stocking density and feeding rate
significantly impact growth and egg production in female medaka.

Host Factors in Chemical Carcinogenesis
We have seen that environmental abiotic factors such as the temperature, type of carcinogen, duration
of exposure, time of exposure onset, etc., can drastically impact the expression of tumors in fishes.
Conversely, biotic factors of the fish also appear capable of playing a significant role in carcinogenesis
in fishes.

Sex
As discussed earlier, significant body and liver weight differences between male and female medaka
have been observed (Teh and Hinton, 1998), with females growing at a faster rate than males and
achieving a greater liver weight than their male counterparts. In addition, differences were found in
tumor incidence (females higher) following carcinogen (DEN) exposure (Cooke and Hinton, 1999; Teh
and Hinton, 1998). Similar sex-specific results were seen when Reddy et al. (1999a) exposed medaka
to dibenzo(a,l)pyrene. Life-span studies were conducted on spontaneous tumor development in medaka
in outdoor culture ponds (Masahito et al., 1989). The data indicated a particular susceptibility of older
female medaka to liver tumor, but not to any other type of tumor development. Incidence was higher in
females than in males from 3 to 5 years of age, reaching 7.1% in 5-year-old female stock (Masahito et
al., 1989). The fact that these studies showed clear sex differences (females were more responsive) when
others using the same carcinogen (DEN) have not (Brown-Peterson et al., 1999) may be due to differences
in husbandry practices, the genetic background of medaka, and the compound to which they were
exposed. Toussaint et al. (1999), for example, using a chronic bioassay, exposed medaka to a complex
environmental mixture (contaminated groundwater) after initiating the fish with DEN. Treatment resulted
in greater tumor incidence in male than female fish (Kissling et al., 2006). Propanediol, when fed, proved
to be a multisite carcinogen in both sexes of rats and mice, but it caused increased liver tumors only in
male guppies and male medaka (Gunnels et al., 2005).
The same husbandry factors that affect growth may also affect the onset of sexual maturation and
reproductive performance. Results from the stocking density study reviewed above demonstrated signif-
icantly lower body weights and daily egg production in female medaka reared at high vs. low stocking
densities (Davis et al., 2002). Also, body weight and daily egg production were further reduced when,
with stocking density held constant, the feeding rate was reduced from excessive feeding (20% of body
weight daily up to 8 weeks of age, then 15% of body weight daily thereafter) to mildly restrictive (10
to12% of body weight daily up to 6 weeks of age, then 5% of body weight daily thereafter). The Davis
et al. study (2002) demonstrated that the basic husbandry practices of stocking density and feeding rate
significantly impact growth and egg production in female medaka. Interestingly, stocking density or
feeding rate did not significantly affect male body weights; thus, husbandry practices may influence
males and females differently, and, to the extent that sex factors may influence study outcome, husbandry
factors are important sources of variability. It is possible that sex-associated differences may be masked
because of the common practices of heavy stocking in combination with low feeding rates. Under such
conditions, females may not have adequate space and food for maximal growth and reproductive
development (Davis et al., 2002).

Species Differences
Species-specific differences are frequently observed between fishes, rodents, and higher mammals,
including humans. As our review of the trout model has shown, these vertebrates are particularly sensitive
to AFB ; however, in monkey and human liver preparations, the major microsomal biotransformation
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product of AFB is aflatoxin Q , and this product proved 100 times less carcinogenic than AFB in the
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trout model. These studies demonstrated species differences in the metabolism of the procarcinogen
(Hendricks et al., 1980). Trout exhibit only limited capacity for DNA repair, especially for removal of
bulky DNA adducts (Bailey et al., 1988).