Ochratoxin A: In utero exposure in mice induces adducts in testicular DNA

Jamie E. Jennings-Gee, Mariana Tozlovanu, Richard Manderville, Mark Steven Miller, Annie Pfohl-Leszkowicz, Gary G. Schwartz

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Ochratoxin A (OTA) is a nephrotoxin and carcinogen that is associated with Balkan endemic nephropathy and urinary tract tumors. OTA crosses the placenta and causes adducts in the liver and kidney DNA of newborns. Because the testis and kidney develop from the same embryonic tissue, we reasoned that OTA also may cause adducts transplacentally in the testis. We tested the hypothesis that acute exposure to OTA, via food and via exposure in utero, causes adducts in testicular DNA and that these lesions are identical to those that can be produced in the kidney and testis by the consumption of OTA. Adult mice received a single dose of OTA (from 0-1,056 μg/kg) by gavage. Pregnant mice received a single i.p. injection of OTA (2.5 mg/kg) at gestation day 17. DNA adducts were determined by 32P-postlabeling. Gavage-fed animals sacrificed after 48 hours accumulated OTA in kidney and testis and showed DNA adducts in kidney and testis. Some OTA metabolites isolated from the tissues were similar in both organs (kidney and testis). The litters of mice exposed prenatally to OTA showed no signs of overt toxicity. However, newborn and 1-month old males had DNA adducts in kidney and testis that were chromatographically similar to DNA adducts observed in the kidney and testis of gavage-fed adults. One adduct was identified previously as C8-dG-OTA adduct by LC MS/MS. No adducts were observed in males from dams not exposed to OTA. Our findings that in utero exposure to OTA causes adducts in the testicular DNA of male offspring support a possible role for OTA in testicular cancer.

Original languageEnglish (US)
Pages (from-to)1428-1444
Number of pages17
JournalToxins
Volume2
Issue number6
DOIs
StatePublished - Jun 1 2010

Fingerprint

DNA
Testis
Kidney
DNA Adducts
ochratoxin A
Balkan Nephropathy
Tissue
Testicular Neoplasms
Metabolites
Urinary Tract
Carcinogens
Liver
Placenta
Dams
Toxicity
Tumors
Animals
Food
Pregnancy
Injections

Keywords

  • DNA adduct
  • Epidemiology
  • Ochratoxin
  • Testicular cancer
  • Transplacental contamination

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Jennings-Gee, J. E., Tozlovanu, M., Manderville, R., Miller, M. S., Pfohl-Leszkowicz, A., & Schwartz, G. G. (2010). Ochratoxin A: In utero exposure in mice induces adducts in testicular DNA. Toxins, 2(6), 1428-1444. https://doi.org/10.3390/toxins2061428

Ochratoxin A : In utero exposure in mice induces adducts in testicular DNA. / Jennings-Gee, Jamie E.; Tozlovanu, Mariana; Manderville, Richard; Miller, Mark Steven; Pfohl-Leszkowicz, Annie; Schwartz, Gary G.

In: Toxins, Vol. 2, No. 6, 01.06.2010, p. 1428-1444.

Research output: Contribution to journalArticle

Jennings-Gee, JE, Tozlovanu, M, Manderville, R, Miller, MS, Pfohl-Leszkowicz, A & Schwartz, GG 2010, 'Ochratoxin A: In utero exposure in mice induces adducts in testicular DNA', Toxins, vol. 2, no. 6, pp. 1428-1444. https://doi.org/10.3390/toxins2061428
Jennings-Gee JE, Tozlovanu M, Manderville R, Miller MS, Pfohl-Leszkowicz A, Schwartz GG. Ochratoxin A: In utero exposure in mice induces adducts in testicular DNA. Toxins. 2010 Jun 1;2(6):1428-1444. https://doi.org/10.3390/toxins2061428
Jennings-Gee, Jamie E. ; Tozlovanu, Mariana ; Manderville, Richard ; Miller, Mark Steven ; Pfohl-Leszkowicz, Annie ; Schwartz, Gary G. / Ochratoxin A : In utero exposure in mice induces adducts in testicular DNA. In: Toxins. 2010 ; Vol. 2, No. 6. pp. 1428-1444.
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