Induction of DNA-adducts and increase of 8-hydroxy-2-deoxyguanosine, but no development of preneoplastic lesions in offspring liver with transplacental and trans-breast milk exposure to 2-amino-3,8-dimethylimidazo [4,5-f ]quinoxaline (MeIQx) in rats.
Humans may be exposed to 2-amino-3,8-dimethylimidazo[4,5-f ]quinoxaline (MeIQx) at low doses during the period of gestation and lactation, and thereafter throughout life. The current study was designed to examine the possibility that early exposure may increase the risk of liver tumor development and related genetic changes. Male and female F344 rats were therefore administered MeIQx in diet (1, 10 and 100 ppm) for 4 weeks before mating and also during gestation and lactation. We also examined the carcinogenic risk of low-dose maternal and post-weaning exposure (MeIQx at doses of 1 and 10 ppm). Surviving male F1 rats were sacrificed under ether anesthesia at 19 weeks of age for analyses of glutathione S-transferase placental form-positive foci in the liver and aberrant crypt foci in the colon, as putative preneoplastic lesions. Transplacental and trans-breast milk exposure to MeIQx did not enhance development of the lesions, and levels of cell proliferation in the liver also did not differ from control values. However, excretion of MeIQx into breast milk and transfer to the fetus and offspring were observed with resultant hepatic MeIQx-DNA adducts and 8-hydroxy-2'-deoxyguanosine formation. Thus, our data suggest that maternal exposure to MeIQx during the period of pregnancy and lactation may not increase the risk of hepatocarcinogenesis in male offspring, despite causing genetic damage. If this result can be extrapolated to humans, exposure to MeIQx may not increase carcinogenic risk in offspring at usual human exposure levels.
Ichihara
Toshio
T
Department of Pathology, Osaka City University Medical School, Osaka 545-8585, Japan. ichi@dims.co.jp
Wanibuchi
Hideki
H
Totsuka
Yukari
Y
Morimura
Keiichirou
K
Wei
Min
M
Nakae
Dai
D
Fukushima
Shoji
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D049109:Cell Proliferation; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology; D018736:DNA Adducts / Q000096:biosynthesis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D004032:Diet; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007774:Lactation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology; D008297:Male; D008895:Milk, Human / Q000187:drug effects / Q000201:enzymology; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology; D011247:Pregnancy; D011810:Quinoxalines / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D018736:DNA Adducts; D011810:Quinoxalines; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005982:Glutathione Transferase; D003849:Deoxyguanosine