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Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CDl Mice.
Citation:
Waalkes, M. P., E. J. Tokar, B. A. Diwan, J. M. Ward, AND D. J. THOMAS. Tumors and Proliferative Lesions in Adult Offspring After Maternal Exposure to Methylarsonous Acid During Gestation in CDl Mice. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
This abstract describes the effect of in utero exposure to methylaronous acid on the development of tumors in later life. Methylarsonous acid is found to be a transplacental carcinogen with a pattern of tumor distribution that approximates that found after in utero exposure to inorganic arsenic.
Description:
Inorganic arsenic exposure is carcinogenic in humans and rodents. When pregnant mice are exposed to inorganic arsenic in the drinking water their offspring, when adults, develop tumors and proliferative lesions at several sites, such as lung, liver, adrenal, uterus, ovary and oviduct. There is some suspicion that biomethylation products of inorganic arsenic, such as methylarsonous acid (MMA3+), may be an important carcinogenic species. Thus, we exposed pregnant CDI mice to MMA3+ at 0 (control), 12.5 and 25 parts per million (ppm) in the drinking water from gestation day 8 to 18, stopped exposure and assessed tumors and proliferative lesions in groups (initial n = 25) of male and female offspring until two years of age. These doses did not impact survival or body weights at 104 weeks. Female offspring showed significant increases in total epithelial ovarian tumors (primarily adenoma; control 0%; 12.5 ppm 39%; 25 ppm 26%), adrenal cortical adenoma at 25 ppm (control 0%; 25 ppm 26%) and epithelial uterine tumors at 12.5 ppm (primarily carcinoma; control 0%; 12.5 ppm 22%). Females also showed dose-related increases in oviduct hyperplasia (control 4%; 12.5 ppm 35%; 25 ppm 43%). Male offspring showed an increase in hepatocellular carcinoma at the highest dose (control 0%; 25 ppm 21%), and at the lower dose increased adrenal adenomas (control 0%; 12.5 ppm 28%) and lung adenocarcinoma (control 17%; 12.5 ppm 44%). Male offspring from MMA3+-treated mothers showed some unusual testicular tumors and lesions including 2 rete testis carcinomas, 2 rete testis adenomas, 4 rete testis hyperplasias, 3 testicular interstitial cell tumors, and 2 testicular interstitial cell hyperplasias. Overall, gestational maternal exposure to MMA3+ produces some of the same tumors as similarly applied inorganic arsenic, although the testicular lesions seen in the present work with MMA3+ were not previously observed with inorganic arsenic. (This abstract does not reflect the policies of the U.S. E.P.A.).