Effects of sublethal irradiation on changes in crypts of the mouse colon during treatment with 1,2-dimethylhydrazine.

The effects of low-dose X-irradiation on the progression of early neoplastic changes induced in the colon by 1,2-dimethylhydrazine (DMH) were assessed. Outbred female Swiss-Webster mice were treated with DMH only, DMH-irradiation, irradiation only, or 0.001 M EDTA. Animals were pulsed with [3H]thymidine for 1 hour, and the distal colon was radioautographed. The number of labeled cells per crypt in animals tested with DMH-irradiation was greater (P less than 0.01) than the number in "DMH-only" animals, but a corresponding increase in the length of the crypts did not occur. After 16 weeks of treatment, the percentage of animals with focal atypia was similar in the DMH-irradiation group (87%), and the DMH-only group (100%), but there were more focal atypias per animal in the DMH-only group. After 20 weeks, 14% of the DMH-irradiation group had visible tumors compared to 63% of the DMH-only group. The results suggest that DMH increased the number of cells at risk for irradiation; thus the surge in proliferation subsequent to cell depletion was amplified. However, the development of precancerous lesions was not promoted.

Immunocytochemical localization of estrogen receptors in the macaque reproductive tract with monoclonal antiestrophilins.

Monoclonal antibodies to the estrogen receptor (anti-ER) were used to develop an immunocytochemical method to detect ERs in frozen sections of the macaque reproductive tract. Specific nuclear, but not cytoplasmic, staining occurred with two different methods: direct, in which an antiestrophilin -horseradish peroxidase conjugate was used as the first antibody, and indirect, in which a mixture of antiestrophilins was used in the first incubation step. Nuclear staining was absent when various control antibodies replaced the anti-ER. In uteri from spayed monkeys treated with estradiol (E2) for 14 days, nuclear staining was always present. In uteri from similar animals treated for an additional 14 days with E2 and progesterone, nuclear staining was almost completely absent. Mean endometrial nuclear ER levels, measured by an exchange assay, were 5-fold greater in the E2-treated than in the E2-plus progesterone-treated group. In addition, when samples of estrogenized uterus and oviduct were incubated for 60 min in vitro with 100 nM E2, the intensity of nuclear staining increased in parallel with an increase in the concentration of nuclear ER. The nuclei of stromal, smooth muscle, and epithelial cells of the estrogenized oviduct, cervix, and vagina as well as smooth muscle cells of the estrogenized myometrium were also receptor positive. Nontarget tissues, such as duodenum, colon, esophagus, and skeletal muscle, contained no cells that showed specific nuclear staining. Some staining of cytoplasmic and extracellular components occurred in all preparations. These latter reactions were nonspecific, because they were present in many nontarget tissues or when control antibodies replaced the anti-ER. With current methods, only nuclear ERs can be reliably localized in frozen sections of monkey tissues with monoclonal antiestrophilins .

Monoclonal antibody COL-1 reacts with restricted epitopes on carcinoembryonic antigen: an immunohistochemical study.

We used a monoclonal antibody, MAb COL-1, which recognized a restricted epitope on the carcinoembryonic antigen (CEA) molecule, to stain a wide variety of human normal and cancerous tissues. None of the 35 different types of normal tissue stained with COL-1. Of 59 types of benign and malignant tissues, COL-1 reacted with neoplasms of epithelial origin, especially the gastrointestinal tract, breast, lung, and bladder. In benign adenomatous colon polyps, villous adenomas were more frequently stained than tubular adenomas. Normal colon tissue from individuals without colon disease was unreactive, but very weak reactivity was noted in normal-appearing mucosa several centimeters remote from colon cancers. In contrast, another anti-CEA antibody with a less restricted epitope reacted frequently with both normal and remote colon mucosa. These results indicate that MAb COL-1 recognizes a restricted CEA epitope expressed only on pre-malignant or malignant cells and therefore may be a useful reagent for immunopathology.