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.
Full Text
The Full Text of this article is available as a PDF (552.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson L. M., Diwan B. A., Fear N. T., Roman E. Critical windows of exposure for children's health: cancer in human epidemiological studies and neoplasms in experimental animal models. Environ Health Perspect. 2000 Jun;108 (Suppl 3):573–594. doi: 10.1289/ehp.00108s3573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Andersson S. O., Baron J., Wolk A., Lindgren C., Bergström R., Adami H. O. Early life risk factors for prostate cancer: a population-based case-control study in Sweden. Cancer Epidemiol Biomarkers Prev. 1995 Apr-May;4(3):187–192. [PubMed] [Google Scholar]
- Baxter R. C. Insulin-like growth factor binding proteins as glucoregulators. Metabolism. 1995 Oct;44(10 Suppl 4):12–17. doi: 10.1016/0026-0495(95)90215-5. [DOI] [PubMed] [Google Scholar]
- Campbell J. H., Perkins P. Transgenerational effects of drug and hormonal treatments in mammals: a review of observations and ideas. Prog Brain Res. 1988;73:535–553. doi: 10.1016/S0079-6123(08)60525-7. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P. DNA methylation, genomic imprinting and cancer. Curr Top Microbiol Immunol. 2000;249:87–99. doi: 10.1007/978-3-642-59696-4_6. [DOI] [PubMed] [Google Scholar]
- Frame L. T., Hart R. W., Leakey J. E. Caloric restriction as a mechanism mediating resistance to environmental disease. Environ Health Perspect. 1998 Feb;106 (Suppl 1):313–324. doi: 10.1289/ehp.98106s1313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Huang H., Rajkumar K., Murphy L. J. Expression of insulin-like growth factor binding proteins (IGFBPs) in IGFBP-1 transgenic mice. J Endocrinol. 1997 Jan;152(1):99–108. doi: 10.1677/joe.0.1520099. [DOI] [PubMed] [Google Scholar]
- Hursting S. D., Kari F. W. The anti-carcinogenic effects of dietary restriction: mechanisms and future directions. Mutat Res. 1999 Jul 15;443(1-2):235–249. doi: 10.1016/s1383-5742(99)00021-6. [DOI] [PubMed] [Google Scholar]
- Iwasaki T., Hashimoto N., Endoh D., Imanisi T., Itakura C., Sato F. Life span and tumours in the first-generation offspring of the gamma-irradiated male mouse. Int J Radiat Biol. 1996 Apr;69(4):487–492. doi: 10.1080/095530096145788. [DOI] [PubMed] [Google Scholar]
- Janerich D. T., Hayden C. L., Thompson W. D., Selenskas S. L., Mettlin C. Epidemiologic evidence of perinatal influence in the etiology of adult cancers. J Clin Epidemiol. 1989;42(2):151–157. doi: 10.1016/0895-4356(89)90088-7. [DOI] [PubMed] [Google Scholar]
- Kari F. W., Dunn S. E., French J. E., Barrett J. C. Roles for insulin-like growth factor-1 in mediating the anti-carcinogenic effects of caloric restriction. J Nutr Health Aging. 1999;3(2):92–101. [PubMed] [Google Scholar]
- Lee P. D., Giudice L. C., Conover C. A., Powell D. R. Insulin-like growth factor binding protein-1: recent findings and new directions. Proc Soc Exp Biol Med. 1997 Dec;216(3):319–357. doi: 10.3181/00379727-216-44182. [DOI] [PubMed] [Google Scholar]
- Loktionov A., Popovich I., Zabezhinski M., Martel N., Yamasaki H., Tomatis L. Transplacental and transgeneration carcinogenic effect of 7,12-dimethylbenz[a]anthracene: relationship with ras oncogene activation. Carcinogenesis. 1992 Jan;13(1):19–24. doi: 10.1093/carcin/13.1.19. [DOI] [PubMed] [Google Scholar]
- McCarty M. F. Up-regulation of IGF binding protein-1 as an anticarcinogenic strategy: relevance to caloric restriction, exercise, and insulin sensitivity. Med Hypotheses. 1997 Apr;48(4):297–308. doi: 10.1016/s0306-9877(97)90098-0. [DOI] [PubMed] [Google Scholar]
- McKenna I. M., Ramakrishna G., Diwan B. A., Shiao Y. H., Kasprzak K. S., Powell D. A., Anderson L. M. K-ras mutations in mouse lung tumors of extreme age: independent of paternal preconceptional exposure to chromium(III) but significantly more frequent in carcinomas than adenomas. Mutat Res. 2001 Jan 25;490(1):57–65. doi: 10.1016/s1383-5718(00)00153-4. [DOI] [PubMed] [Google Scholar]
- Olsen J. H., de Nully Brown P., Schulgen G., Jensen O. M. Parental employment at time of conception and risk of cancer in offspring. Eur J Cancer. 1991;27(8):958–965. doi: 10.1016/0277-5379(91)90258-f. [DOI] [PubMed] [Google Scholar]
- Pavelic K., Hrsak I. Effect of immunosuppression on the growth of six murine tumors. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1978 Sep 28;92(2):147–156. doi: 10.1007/BF00312407. [DOI] [PubMed] [Google Scholar]
- Pollak M. Insulin-like growth factor physiology and cancer risk. Eur J Cancer. 2000 Jun;36(10):1224–1228. doi: 10.1016/s0959-8049(00)00102-7. [DOI] [PubMed] [Google Scholar]
- Potischman N., Troisi R. In-utero and early life exposures in relation to risk of breast cancer. Cancer Causes Control. 1999 Dec;10(6):561–573. doi: 10.1023/a:1008955110868. [DOI] [PubMed] [Google Scholar]
- Ruggeri B. A., Klurfeld D. M., Kritchevsky D., Furlanetto R. W. Caloric restriction and 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in rats: alterations in circulating insulin, insulin-like growth factors I and II, and epidermal growth factor. Cancer Res. 1989 Aug 1;49(15):4130–4134. [PubMed] [Google Scholar]
- Sapolsky R. M., Romero L. M., Munck A. U. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev. 2000 Feb;21(1):55–89. doi: 10.1210/edrv.21.1.0389. [DOI] [PubMed] [Google Scholar]
- Schoen R. E., Tangen C. M., Kuller L. H., Burke G. L., Cushman M., Tracy R. P., Dobs A., Savage P. J. Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst. 1999 Jul 7;91(13):1147–1154. doi: 10.1093/jnci/91.13.1147. [DOI] [PubMed] [Google Scholar]
- Sephton S. E., Sapolsky R. M., Kraemer H. C., Spiegel D. Diurnal cortisol rhythm as a predictor of breast cancer survival. J Natl Cancer Inst. 2000 Jun 21;92(12):994–1000. doi: 10.1093/jnci/92.12.994. [DOI] [PubMed] [Google Scholar]
- Tomatis L., Narod S., Yamasaki H. Transgeneration transmission of carcinogenic risk. Carcinogenesis. 1992 Feb;13(2):145–151. doi: 10.1093/carcin/13.2.145. [DOI] [PubMed] [Google Scholar]
- Tomatis L. Transgeneration carcinogenesis: a review of the experimental and epidemiological evidence. Jpn J Cancer Res. 1994 May;85(5):443–454. doi: 10.1111/j.1349-7006.1994.tb02378.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Turusov V. S., Nikonova T. V., Parfenov YuD Increased multiplicity of lung adenomas in five generations of mice treated with benz(a)pyrene when pregnant. Cancer Lett. 1990 Dec 17;55(3):227–231. doi: 10.1016/0304-3835(90)90123-f. [DOI] [PubMed] [Google Scholar]
- Yu H., Rohan T. Role of the insulin-like growth factor family in cancer development and progression. J Natl Cancer Inst. 2000 Sep 20;92(18):1472–1489. doi: 10.1093/jnci/92.18.1472. [DOI] [PubMed] [Google Scholar]
- Yu W., Sipowicz M. A., Haines D. C., Birely L., Diwan B. A., Riggs C. W., Kasprzak K. S., Anderson L. M. Preconception urethane or chromium(III) treatment of male mice: multiple neoplastic and non-neoplastic changes in offspring. Toxicol Appl Pharmacol. 1999 Jul 15;158(2):161–176. doi: 10.1006/taap.1999.8692. [DOI] [PubMed] [Google Scholar]