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Treatment of calf thymus DNA with various types of asbestos fibers in the presence of hydrogen peroxide under physiological conditions (pH 7.4, 37 degrees) resulted in the hydroxylation of the C-8 position of guanine residues. DNA strand scission was also detected after these treatments.

The effect of crude stomach extracts (CSE) on X-ray-induced gastric tumorigenesis was examined. ICR mice were treated with two or four administrations of CSE at one-week intervals then irradiated with 20 Gy of X-rays one week after the final CSE administration. Unexpectedly, the incidence of X-ray-induced tumors was not significantly altered by two CSE pretreatments but was markedly reduced by four CSE pretreatments. Similarly, erosion and squamous metaplasia produced in the glandular stomach a week after X-irradiation were markedly diminished by four CSE pretreatments but not by two CSE pretreatments.

The potential carcinogenicity of captafol in B6C3F1 mice was examined. Captafol was given at levels of 0 (control), 0.075, 0.15 or 0.3% in the diet to a total of 203 males and 203 females for 96 weeks, after which time the animals were returned to basal diet for a further 8 weeks. Mice surviving 42 weeks or longer were included in the effective numbers. Males and females given 0.3% captafol showed increased cumulative mortalities in the final quarter period of the experiment. Significant increases in the development of neoplastic lesions were found in the heart, spleen, forestomach, small intestine and liver of mice of both sexes treated with captafol. Tumors induced by captafol were, histologically, hemangioendothelioma in the heart, hemangioma or hemangioendothelioma in the spleen, papilloma and squamous cell carcinoma in the forestomach, adenoma and adenocarcinoma in the small intestine, and hyperplastic nodule and hepatocellular carcinoma in the liver. These results demonstrate a broad-spectrum carcinogenicity of captafol in B6C3F1 mice.

The nature of the in vivo anti-tumor effector cells was investigated in two different tumor system, MH134 hepatoma and X5563 plasmacytoma, in which tumor-specific antibodies and cytotoxic T lymphocytes (CTL), respectively, mediate in vitro tumor cell lyses. Winn assays utilizing MH134- and X5563-immune spleen cells revealed that in both tumor systems, tumor neutralization was produced exclusively by a tumor-specific immune Lyt-1 T cell subpopulation which was depleted of antibody-producing B cells or T cell subset(s) capable of generating CTL responses. These Lyt-1 T cells could exert their in vivo tumor-protective function under conditions in which MH134 tumor-specific antibody was not detected or in T cell-depleted recipient mice (B cell mice) in which CTL precursors were not recruited, indicating that their activities do not depend on the induction of antibody or CTL response. These results are discussed in the context of the relationships (1) between effector systems detected in in vitro cytotoxicity tests and effector mechanisms responsible for in vivo tumor protection, and (2) between epitopes or molecules required for triggering in vitro and in vivo effectors against the tumor.

The effects of three sweeteners, sodium saccharin, aspartame and stevioside, on urinary bladder carcinogenesis in rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were evaluated. Male F344 rats were given 0.01% BBN in their drinking water for 4 weeks and then the test sweeteners in their diet for 32 weeks. All surviving rats were sacrificed after 36 weeks, and examined histologically. Treatment with sodium saccharin significantly increased the incidence and extent of preneoplastic lesions, papillary or nodular (PN) hyperplasia, in rats treated with BBN for 4 weeks. Administration of 5% aspartame or 5% stevioside in the diet did not, however, affect the incidence or extent of PN hyperplasia in BBN-treated rats. No preneoplastic or neoplastic lesions of the urinary bladder were observed in rats treated with the test sweeteners only. The results with sodium saccharin were consistent with those in our previous experiments. The data also suggest that aspartame and stevioside do not promote bladder carcinogenesis.

The promoting effects of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and sodium L-ascorbate on two-stage carcinogenesis initiated with methylnitrosourea (MNU) in F344 male rats were investigated. Animals were given injections of MNU (20 mg/kg ip) twice a week for 4 weeks, and then basal diet containing 2% BHA, 1% BHT or 5% sodium L-ascorbate for the next 32 weeks. Administration of BHA, BHT or sodium L-ascorbate in the diet significantly increased the incidences per group and numbers per rat of papilloma and papillary or nodular hyperplasia of the urinary bladder, and BHA and BHT also increased the number of cancers per rat. Furthermore BHA significantly increased the incidences of cancer and papilloma in the forestomach of rats initiated with MNU, whereas treatment with BHA alone was associated with papilloma but no carcinoma development in the rat forestomach. The incidence of adenoma, but not adenocarcinoma, of the thyroid was significantly increased by treatment with MNU plus BHT. These results show that BHA, BHT and sodium L-ascorbate have promoting activities on urinary bladder carcinogenesis in rats initiated with MNU, and that BHA also has a promoting effect on forestomach carcinogenesis after initiation with MNU.

The reactivity of alpha-fetoprotein (AFP) with concanavalin A (Con A) and Lens culinaris agglutinin (LCA) was studied by crossed immuno-affinoelectrophoresis of the serum samples of 146 patients from three groups (groups I, II and III). Fifty-one patients with benign liver diseases were included in group I, 83 patients with hepatocellular carcinoma in group II, and 12 patients with carcinoma metastatic to the liver from digestive organs in group III. In group I, the percentage of Con A-reactive species of AFP was high (97 +/- 5%, mean +/- SD), but that of LCA-reactive species was very low (3 +/- 5%). The percentage of LCA-reactive species of AFP in group II (45 +/- 33%) was higher than that in group I (P less than 0.001), while the Con A binding pattern of AFP in this group, as demonstrated by immuno-affinoelectrophoresis, was similar to that of group I. The percentage of Con A-reactive species of AFP in group III (55 +/- 24%) was much lower than that in group II (97 +/- 5%) (P less than 0.001). The above results indicate that measurement of the reactivity of AFP in serum samples with Con A and LCA is useful for the differentiation of AFP species which are found in association with benign liver diseases, hepatocellular carcinoma and carcinoma metastatic to the liver.

Massive abdominal enlargement was observed at relatively high incidence in two species of fish kept in two public aquariums for several years. Three seminomas, one dysgerminoma and two fibromas were found in 14 largemouth bass, Micropterus salmoides, kept in a public aquarium for over 80 months. Four seminomas and one nephroblastoma were found in 24 Japanese dace (ugui), Tribolodon hakonensis, kept for more than 57 months in two different aquariums. The seminomas in M. salmoides showed rapid growth, and the affected fish died within a few months. At necropsy, a single large tumor, measuring 10.5-12.0 cm, was found in the abdominal cavity. The seminomas in T. hakonensis were single or multiple tumors, measuring 2.0-4.5 cm in diameter. Histologically, these seminomas were composed mainly of a typical germ cells similar to those in human seminomas or embryonal carcinomas. A nephroblastoma in one T. hakonensis showed extensive metastases to various organs. The cause of these tumors is unknown, but the prolonged longevity of fish kept under artificial conditions may have enhanced their development.

A 41-kilodalton protein was detected in four human T-cell leukemia virus type I (HTLV-I)-infected cell lines, a 68-kilodalton glycoprotein in MT-2 cells, and a 38-kilodalton protein in an HTLV-II-infected cell line by using antibody against a synthetic dodecapeptide, a portion of the polypeptide deduced from the nucleotide sequence of the X regions of HTLVs.

Spontaneous tumors of the nervous system and associated organs and/or tissues in 346 male and 346 female F344/DuCrj rats and 200 male and 177 female Slc:Wistar rats were examined. The main neurogenic tumors observed were gliomas and neurinomas, which were detected in both strains of rats. Out of 7 gliomas, 6 were found in the brain and 1 in the spinal cord, and out of 4 neurinomas, 2 were in the trigeminal nerves and the other 2 were in the spinal nerves. In addition, other types of tumors (2 granular cell tumors in the brain, 1 pinealoma, 3 ganglioneuromas in the adrenal gland, 1 undifferentiated carcinoma in the nasal cavity and 1 chordoma in the posterior neck region) were observed.