Open AccessInduction 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 (MelQx) in rats
Author(s) -
Ichihara Toshio,
Wanibuchi Hideki,
Totsuka Yukari,
Morimura Keiichirou,
Wei Min,
Nakae Dai,
Fukushima Shoji
Publication year - 2004
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2004.tb03181.x
Subject(s) - transplacental , deoxyguanosine , offspring , breast milk , chemistry , medicine , dna , biology , pregnancy , biochemistry , genetics , fetus , placenta
Humans may be exposed to 2‐amino‐3,8‐dimethylimidazo[4,5‐flquinoxaline (MelQx) 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 MelQx 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 (MelQx 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 MelQx 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 MelQx into breast milk and transfer to the fetus and offspring were observed with resultant hepatic MelQx‐DNA adducts and 8‐hydroxy‐2′‐deox‐yguanosine formation. Thus, our data suggest that maternal exposure to MelQx 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 MelQx may not increase carcinogenic risk in offspring at usual human exposure levels.