TY - JOUR
T1 - Quantitative carcinogenesis and dosimetry in rainbow trout for aflatoxin B1 and aflatoxicol, two aflatoxins that form the same DNA adduct
AU - Bailey, George S.
AU - Loveland, Patricia M.
AU - Pereira, au Cliff
AU - Pierce, Donald
AU - Hendricks, Jerry D.
AU - Groopman, John D.
N1 - Funding Information:
We thank Dan Arbogast, Ted Will, and Sheila Cleveland for assistance in care and maintenance of trout, and Jean Barnhill and Connie Owston for histological slide preparation. This work was partially supported through Public Health Grants grants ES04766, ES03850 and ES00210 from the National Institute of Environmental Health Sciences. This is technical paper number 10,412 from the Oregon State University Agricultural Experiment Station.
PY - 1994/8
Y1 - 1994/8
N2 - Two exposure protocols were used to establish complete dose-response relationships for the hepatic carcinogenicity and DNA adduction in vivo of aflatoxin B1 (AFB1) and aflatoxicol (AFL) in rainbow trout. By passive egg exposure, AFL was taken up less well than AFB1, but was more efficiently sequestered into the embryo itself, to produce an embryonic DNA bibding curve that was linear with carcinogen dose and with a DNA binding index three-fold greater than AFB1. Both aflatoxins produced the same phenotypic response, predominantly mixed hepatocellular/cholangiocellular carcinoma. Tumor responses as logit [incidince] vs. In [dose] were parallel-offset, non-linear responses showing a three-fold greater carcinogenic potency for AFL at all doses examined (i.e. 3 times more AFB1 than AFL required to produce an equivalent liver tumor incidence). By molecular dosimetry analysis (logit [incidence] vs. In [DNA adducts]), the two data sets were coincident, indicating that, per DNA adduct formed in vivo in total embryonic DNA, these two aflatoxins were equally efficient in tumor initiation. By dietary fry exposure, both carcinogens produced linear DNA binding dose responses in liver, but with an AFL target organ DNA binding index only 1.14 times that of AFB1 by this exposure route. The tumor dose-response curves also did not exhibit the three-fold difference shown by embryo exposure, but were closely positioned non-linear curves. Since the DNA binding indices differed by only 14%, the resulting molecular dosimetry curves for AFL and AFB1 by dietary exposure were similar to the tumor response curves. These results indicate that differing exposure routes produced differing relative carcinogenicity estimates based on doses appllied result of protocol-dependent differences in AFL and AFB1 pharmacokinetic behaviors, but that potency comparisons based on molecular dose received were similar for the two protocols. By comparison with standard DNA adducts produced in vitro using the dimethyloxirane-produced 8,9-epoxides of AFB1 and AFL, we conclude that > 99% of AFL-DNA adducts produced in vivo were identical to those produced by AFB1. Thus similar molecular dosimetry responses should be expected under all exposure protocols in which the two parent carcinogens do not exhibit differing toxicities to the target organ.
AB - Two exposure protocols were used to establish complete dose-response relationships for the hepatic carcinogenicity and DNA adduction in vivo of aflatoxin B1 (AFB1) and aflatoxicol (AFL) in rainbow trout. By passive egg exposure, AFL was taken up less well than AFB1, but was more efficiently sequestered into the embryo itself, to produce an embryonic DNA bibding curve that was linear with carcinogen dose and with a DNA binding index three-fold greater than AFB1. Both aflatoxins produced the same phenotypic response, predominantly mixed hepatocellular/cholangiocellular carcinoma. Tumor responses as logit [incidince] vs. In [dose] were parallel-offset, non-linear responses showing a three-fold greater carcinogenic potency for AFL at all doses examined (i.e. 3 times more AFB1 than AFL required to produce an equivalent liver tumor incidence). By molecular dosimetry analysis (logit [incidence] vs. In [DNA adducts]), the two data sets were coincident, indicating that, per DNA adduct formed in vivo in total embryonic DNA, these two aflatoxins were equally efficient in tumor initiation. By dietary fry exposure, both carcinogens produced linear DNA binding dose responses in liver, but with an AFL target organ DNA binding index only 1.14 times that of AFB1 by this exposure route. The tumor dose-response curves also did not exhibit the three-fold difference shown by embryo exposure, but were closely positioned non-linear curves. Since the DNA binding indices differed by only 14%, the resulting molecular dosimetry curves for AFL and AFB1 by dietary exposure were similar to the tumor response curves. These results indicate that differing exposure routes produced differing relative carcinogenicity estimates based on doses appllied result of protocol-dependent differences in AFL and AFB1 pharmacokinetic behaviors, but that potency comparisons based on molecular dose received were similar for the two protocols. By comparison with standard DNA adducts produced in vitro using the dimethyloxirane-produced 8,9-epoxides of AFB1 and AFL, we conclude that > 99% of AFL-DNA adducts produced in vivo were identical to those produced by AFB1. Thus similar molecular dosimetry responses should be expected under all exposure protocols in which the two parent carcinogens do not exhibit differing toxicities to the target organ.
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U2 - 10.1016/0165-1161(94)90030-2
DO - 10.1016/0165-1161(94)90030-2
M3 - Article
C2 - 7519308
AN - SCOPUS:0027956943
SN - 0165-1161
VL - 313
SP - 25
EP - 38
JO - Mutation Research/Environmental Mutagenesis and Related Subjects
JF - Mutation Research/Environmental Mutagenesis and Related Subjects
IS - 1
ER -