DNA adducts and induction of sister chromatid exchanges in the rat following benzo[b]fluoranthene administration.
Benzo[b]fluoranthene (B[b]F) was administered (100 mg/kg by i.p. injection) to male Sprague--Dawley rats. Lungs, livers and peripheral blood lymphocytes (PBLs) were harvested 1, 3, 5, 7, 14, 28 and 56 days after treatment. Several DNA adducts were observed in each tissue, with maximal levels occurring at approximately 7 days after treatment. Lung DNA exhibited consistently higher adduct levels than liver or PBL DNA. At 56 days after B[b]F administration, the adducts in liver and PBL DNA were present at < 10 amol/microgram DNA, while in lung there were 100 amoles/microgram DNA. No significant differences were observed between tissues in the types of adducts produced. Co-chromatography with synthetic standards showed that only a minor adduct produced in vivo is derived from trans-9,10-dihydro-9,10-dihydroxybenzo[b]fluoranthene-11,12-oxide. Sister chromatid exchanges (SCEs) from whole blood cultures were significantly increased relative to concurrent controls between 1 and 14 days after B[b]F administration, with maximum levels at 14 days. By 28 days after treatment, SCEs had essentially returned to control levels. SCE induction did not correlate with the amount of B[b]F--DNA adducts remaining in the PBLs at harvest time.
Ross
J A
JA
Carcinogenesis and Metabolism Branch, US Environmental Protection Agency, Research Triangle Park, NC 27711.
Nelson
G B
GB
Holden
K L
KL
Kligerman
A D
AD
Erexson
G L
GL
Bryant
M F
MF
Earley
K
K
Beach
A C
AC
Gupta
R C
RC
Nesnow
S
S
D000818:Animals; D004247:DNA / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D005449:Fluorenes / Q000378:metabolism / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007553:Isotope Labeling; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D010761:Phosphorus Radioisotopes; D011083:Polycyclic Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D005449:Fluorenes; D010761:Phosphorus Radioisotopes; D011083:Polycyclic Compounds; D004247:DNA; C006703:benzo(b)fluoranthene