The age-related difference in bone changes in rats induced by recombinant human granulocyte colony-stimulating factor.
We examined the bone changes in recombinant granulocyte colon-stimulating factor (rhG-CSF)-treated young and young adult rats in order to investigate the effect of age-related conditions of bone growth on the bone changes induced by rhG-CSF. Recombinant human G-CSF (100 and 1,000 micrograms/kg/day) was given to rats by daily intravenous injection for 28 days starting at the age of either 6 or 14 wk, and the hindlimb bones were evaluated histopathologically. In the young rats, bone lesions were observed in the 100- and 1,000-micrograms/k groups. In the young adult rats, lesions were found only in the 1,000-micrograms/kg group. The lesions involved accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification and there was no age-related difference in these histopathological findings. However, both the incidence of bone involvement and the severity of lesions were greater in the young rats than in the dose-matched young adult rats. The results suggest that the higher dose of rhG-CSF may intrinsically induce bone lesions of a particular histopathological nature in rats regardless of their age, and the action of rhG-CSF on bone may be stronger in young growing rats than in young adults.
Suzuki
M
M
Toxicology Research Laboratory, Chugai Pharmaceutical Co., Ltd., Nagano, Japan.
Sakamaki
Y
Y
Miyoshi
A
A
Adachi
K
K
Usami
M
M
Nakayama
H
H
Doi
K
K
D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000473:pathology*; D002118:Calcium / Q000097:blood; D016179:Granulocyte Colony-Stimulating Factor / Q000633:toxicity*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000633:toxicity*
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D002118:Calcium