Abstract
Preconceptional carcinogenesis occurs in animals and is suspected for humans--for example, after occupational metals exposure. Several characteristics in animal models, including high frequency and non-Mendelian inheritance patterns, have suggested an epigenetic mechanism, possibly involving hormone changes in offspring. To test this hypothesis, we treated male mice with chromium(III) chloride, a preconceptional carcinogen, 2 weeks before mating, in two separate experiments. Their 10-week-old offspring showed highly significant increases in average serum corticosterone and glucose, compared with control offspring. Average serum levels of insulin-like growth factor 1 (IGF1) showed more modest possible increases. A previous microarray experiment identified hepatic insulin-like growth factor binding protein 1 (IGF BP1) gene expression as consistently changed in correlation with serum corticosterone levels. In the present study, hepatic IGF BP1 mRNA correlated with serum IGF1 in male offspring of chromium-treated fathers, but not in controls; serum glucose correlated positively with hepatic IGF BP1 in chromium-group offspring but negatively in controls. These results support the hypothesis that preconceptional exposure effects may alter hormones, metabolism, and control of tissue gene expression, probably through epigenetic mechanisms. Risk of neoplasia may be influenced by these changes.