Formation of DNA adducts in tissues of mouse progeny through transplacental contamination and/or lactation after administration of a single dose of ochratoxin A to the pregnant mother.
Ochratoxin A (OTA) is a mycotoxin which has been detected in foods of plant origin, in edible animal tissues, and in human sera, urine, and milk in many countries. OTA is nephrotoxic and carcinogenic in mice and rats and is suspected to play a key role in the etiology of Balkan endemic nephropathy and/or associated urinary tract tumors. In the present study, some early signs of genetic impairment, including the presence of DNA adducts in target tissues from the progeny of mice after administration of a single OTA dose during late pregnancy, have been investigated. By the 32P-postlabeling method, several characteristic DNA adducts with the same Rf values were detected in kidney and liver of both the OTA-treated mice and their progeny the fetus and the offspring. No adduct was found in tissues from control animals. Different adducts were most important in kidney and liver DNA and some were organ-specific. High levels of DNA adducts were detected in the kidneys of male progeny, whereas in the female progeny and the mothers they were detected almost exclusively in the liver. This result correlates well with the carcinogenicity in mice: the target organ for males is the kidney, while for females it is the liver. High levels of DNA adducts were also found in fetuses. These results provide evidence for a direct genotoxic action of OTA in the progeny through transplacental contamination, which constitutes a new serious health hazard of exposure to this toxin.
Petkova-Bocharova
T
T
National Oncological Centre, Sofia, Bulgaria.
Stoichev
I I
II
Chernozemsky
I N
IN
Castegnaro
M
M
Pfohl-Leszkowicz
A
A
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D018736:DNA Adducts; D005260:Female; D005333:Fetus / Q000737:chemistry / Q000187:drug effects; D005506:Food Contamination; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000196:embryology; D007774:Lactation; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000196:embryology; D008297:Male; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D009793:Ochratoxins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D009928:Organ Specificity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D018736:DNA Adducts; D009793:Ochratoxins; C025589:ochratoxin A