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Carcinogen-Protein Complexes in Hamster Colon and Glandular Stomach during Long-Term Administration of 3-Methylcholanthrene¹

The Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

Intragastric administration of 3-methylcholanthrene (MCA) has been reported by others to cause cancers of the glandular stomach and large intestines in an inbred strain of Syrian golden hamsters. In search of the molecular basis of this process, this study examined the diversity of the macromolecules and carcinogen-protein complexes in colon and glandular stomach cytosols during the long-term administration of MCA to the susceptible hamsters. Male hamsters of the inbred strain BIO 87.20 were gastrically intubated with MCA three times weekly for 0, 1, 3, 6, and 9 weeks or with corn oil (vehicle) for 10 weeks. Thereafter, 24 hr following an i.p. injection of [³H]MCA, the cytosols were prepared, and their constituents were resolved extensively according to molecular size by columns of Sephadex G-200 gel.

The carcinogen-protein complexes of the colon and glandular stomach cytosols were of similar and unchanging molecular size distributions during the 9 weeks of administration of MCA. The principal carcinogen-protein complex in both organ cytosols had a molecular weight of 80,000 to 90,000. The formation of the complex appears to require metabolism of the carcinogen, inasmuch as only relatively small amounts of complex of that size were generated in vitro by incubation of the carcinogen with the organ cytosols at 1–4°. The major amount of the complex formed in vivo apparently derived from the two organs per se, rather than from the blood therein, which also contained complex of this same molecular size. The MCA-colon and MCA-glandular stomach systems are among a variety of carcinogen-organ systems, at present 6 in number, in which the principal carcinogen-protein complex has been found in this laboratory to have a similar molecular size.

¹ Supported in part by Grants CA-05945 and CA-21522; Institutional Grants CA-09035, CA-06927, and RR-05539 from the NIH; and an appropriation from the Commonwealth of Pennsylvania.

² To whom requests for reprints should be addressed, at The Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Fox Chase, Philadelphia, Pa. 19111.

Received 11/ 9/77. Accepted 3/13/78.