Emergence of delayed methylmercury toxicity after perinatal exposure in metallothionein-null and wild-type C57BL mice.
BACKGROUND
Although a long latency period of toxicity after exposure to methylmercury (MeHg) is known to exist in humans, few animal studies have addressed this issue. Substantiation of delayed MeHg toxicity in animals would affect the risk evaluation of MeHg.


OBJECTIVE
Our goal in this study was to demonstrate the existence of a latency period in a rodent model in which the toxicity of perinatal MeHg exposure becomes apparent only later in life. Our study included metallothionein (MT) knockout mice because studies have suggested the potential susceptibility of this strain to the neurodevelopmental toxicity of MeHg.


METHODS
Pregnant MT-null and wild-type C57Bl/6J mice were exposed to MeHg through their diet containing 5 mug Hg/g during gestation and early lactation. We examined behavioral functions of the offspring using frequently used paradigms, including open field behavior (OPF), passive avoidance (PA), and the Morris water maze (MM), at ages of 12-13 and 52-53 weeks.


RESULTS
At 12 weeks of age, behavioral effects of MeHg were not detected, except for OPF performance in MeHg-exposed MT-null females. At 52 weeks of age, the MeHg-exposed groups showed poorer performance both in PA and MM, and their OPF activity differed from controls. These effects of MeHg appeared exaggerated in the MT-null strain. The brain Hg concentration had leveled off by 13 weeks of age.


CONCLUSIONS
The results suggest the existence of a long latency period after perinatal exposure to low-level MeHg, in which the behavioral effects emerged long after the leveling-off of brain Hg levels. Hence, the initial toxicologic event responsible for the late effects should have occurred before this leveling-off of brain Hg.
Yoshida
Minoru
M
Faculty of Human Health Sciences, Hachinohe University, Hachinohe, Japan.
Shimizu
Natsuki
N
Suzuki
Megumi
M
Watanabe
Chiho
C
Satoh
Masahiko
M
Mori
Kouki
K
Yasutake
Akira
A
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D018811:Maternal Exposure / Q000009:adverse effects*; D018782:Maze Learning / Q000187:drug effects; D008668:Metallothionein / Q000235:genetics / Q000502:physiology*; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000503:physiopathology*
D008767:Methylmercury Compounds; D008668:Metallothionein