DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in fetal tissues of patas monkeys after transplacental exposure

Shylaja Josyula, Leejane Lu, James Salazar, Pratibha V. Nerurkar, Ann Butler Jones, James J. Grady, Elizabeth G. Snyderwine, Lucy M. Anderson

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Transplacental genotoxicity of the heterocyclic amine food-derived mutagen/carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has been investigated by 32P-postlabeling assay for IQ-DNA adducts in maternal liver, placenta, and several fetal tissues of patas monkeys, after exposure to 15, 35, or 50 mg/kg IQ near the end of gestation or to the highest dose in the first or second trimester. Dose-dependent adduct formation occurred in all tissues, with the highest levels occurring in maternal liver. Adduct amounts were similar among fetal tissues and placenta, except for lower levels in fetal brain and slightly more adducts in fetal liver. Adducts in placenta, fetal liver, lung, kidney, skin, and adrenal gland, but not in maternal liver or fetal brain, increased significantly as gestation progressed. Pretreatment with phenobarbital, which induces CYP enzymes that detoxify IQ, decreased adducts in maternal liver and possibly placenta, but not in fetal tissues. The CYP inducer β-naphthoflavone caused a significant increase in IQ-DNA adducts in fetal lungs. Regression analysis suggested that IQ activation in maternal and fetal liver and possibly placenta contributed to adduct formation in fetal tissues; adducts in pla-centa and/or fetal liver were strong predictors for those in most fetal tissues. The results indicate that exposure of pregnant primates to IQ results in DNA adduct formation in most fetal tissues, especially late in gestation; that upregulation of maternal detoxification does not provide fetal protection; and that adducts in placenta indicate adduct levels in fetal tissues. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)151-160
Number of pages10
JournalToxicology and Applied Pharmacology
Volume166
Issue number3
DOIs
StatePublished - 2000

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Erythrocebus patas
Maternal-Fetal Exchange
Liver
Fetus
Tissue
Placenta
Mothers
2-amino-3-methylimidazo(4,5-f)quinoline
Pregnancy
Brain
Lung
Detoxification
DNA Adducts
DNA-(2-amino-3-methylimidazo(4,5-f)quinoline) adduct
Mutagens
Second Pregnancy Trimester
First Pregnancy Trimester
Phenobarbital
Adrenal Glands
Regression analysis

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in fetal tissues of patas monkeys after transplacental exposure. / Josyula, Shylaja; Lu, Leejane; Salazar, James; Nerurkar, Pratibha V.; Jones, Ann Butler; Grady, James J.; Snyderwine, Elizabeth G.; Anderson, Lucy M.

In: Toxicology and Applied Pharmacology, Vol. 166, No. 3, 2000, p. 151-160.

Research output: Contribution to journalArticle

Josyula, Shylaja ; Lu, Leejane ; Salazar, James ; Nerurkar, Pratibha V. ; Jones, Ann Butler ; Grady, James J. ; Snyderwine, Elizabeth G. ; Anderson, Lucy M. / DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in fetal tissues of patas monkeys after transplacental exposure. In: Toxicology and Applied Pharmacology. 2000 ; Vol. 166, No. 3. pp. 151-160.
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