Carcinogenicity of benzo[a]pyrene and manufactured gas plant residues in infant mice.
The present study determined tumorigenicity, tumor classification and DNA damage induced in infant mice by benzo[a]pyrene (B[a]P) or Manufactured Gas Plant (MGP) residues after a single exposure. Male and female B6C3F1 mice were exposed to B[a]P or MGP residue from a single environmental site (MGP-4) and males were also exposed to MGP residue composite from seven different sites (MGP-M7). At 26, 39 and 52 weeks after exposure tumorigenesis was assessed in lung, forestomach and liver. Formation and persistence of DNA adducts were quantified by 32P-postlabeling. Exposure of males to B[a]P induced liver tumors in a dose and time dependent manner. MGP induced more advanced tumors than B[a]P. Only a single liver tumor was found in MGP-4 treated females. No forestomach and few pulmonary adenomas were induced in males or females. MGP-4, MGP-M7 or B[a]P induced DNA adducts in males and females. Adducts in liver, lung and forestomach peaked on different days and decreased at different rates. At 24 h post-exposure, no significant differences in initial DNA adduct levels occurred in males and females exposed to MGP-4 or B[a]P. Lack of DNA damage (adducted DNA) did not account for non-responsiveness of lung and forestomach in B6C3F1 genders as well as in liver in females. MGP tumorigenicity could not be accounted for solely by B[a]P content nor did it reflect additivity of B[a]P and other carcinogenic polycyclic aromatic hydrocarbons (PAHs) in MGP. Synergy among MGP-PAHs, presence of unidentified carcinogens and/or promoters in MGP may account for MGP potency. The B6C3F1 infant male model is a convenient and rapid assay for assessing MGP liver tumorigenicity and potency.
Rodriguez
L V
LV
University of Texas M.D. Anderson Cancer Center, Department of Molecular Pathology, Houston 77030, USA.
Dunsford
H A
HA
Steinberg
M
M
Chaloupka
K K
KK
Zhu
L
L
Safe
S
S
Womack
J E
JE
Goldstein
L S
LS
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity*; D015197:Carcinogenicity Tests; D003033:Coal Tar / Q000378:metabolism / Q000633:toxicity*; D018736:DNA Adducts / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000378:metabolism
D018736:DNA Adducts; D001564:Benzo(a)pyrene; D003033:Coal Tar