Growth hormone-deficient dwarf animals are resistant to dimethylbenzanthracine (DMBA)-induced mammary carcinogenesis.
Increased plasma IGF-1 has consistently been associated with a variety of human cancers, whereas reduced levels of IGF-1 are associated with increased lifespan in other species. However, the aforementioned relationships are correlational or are derived from animal models that are not specific for growth hormone/IGF-1 excess or deficiency. This study was designed to assess the effects of physiological changes in growth hormone and IGF-1 expression on dimethylbenzanthracine (DMBA)-induced mammary carcinogenesis. At 50 days of age, female heterozygous (dw/+) and growth hormone deficient dwarf (dw/dw) rats of the Lewis strain received a single dose of DMBA (80 micro g/g of body weight) via oral gavage. Animals were assigned to one of four experimental groups: a) heterozygous animals (normal size), b) dwarf animals administered vehicle, c) dwarf animals administered low levels of porcine growth hormone (50 micro g twice daily), and d) dwarf animals administered high levels of porcine growth hormone (200 micro g twice daily). At study termination, heterozygous animals exhibited a 70% incidence of mammary tumors, whereas no tumors were observed in saline-treated dwarf animals. Administration of either 100 micro g or 400 micro g growth hormone/day resulted in a dose dependent increase in incidence of mammary tumors (83 and 100%, respectively). Furthermore, heterozygous animals exhibited 1.5 +/- 0.25 tumors per tumor-bearing animal, whereas dwarf animals administered 100 micro g and 400 micro g growth hormone per day had 1.9 +/- 0.63 and 3.4 +/- 0.83 tumors per animal, respectively. The present study demonstrates that DMBA-induced carcinogenesis is dependent on critical plasma levels of growth hormone and IGF-1, and that growth hormone/IGF-1 deficient animals are resistant to DMBA-induced carcinogenesis.
Ramsey
Melinda M
MM
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1083, USA.
Ingram
Rhonda L
RL
Cashion
Adrienne B
AB
Ng
Amy H
AH
Cline
J Mark
JM
Parlow
A F
AF
Sonntag
William E
WE
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D004392:Dwarfism / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000172:deficiency*; D006579:Heterozygote; D007113:Immunity, Innate; D007334:Insulin-Like Growth Factor I / Q000172:deficiency; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone