Gary L. Curtis

Antibody stimulation of benzo(a)pyrene carcinogenesis.

Benzo(a)pyrene (BP) was conjugated to horse serum albumin (HSA) and then attached to aldehyde fixed human erythrocytes. These cells were used in a passive hemagglutination test to measure BP antibody. BP antibodies were found to be induced in Swiss mice injected with tumorigenic doses of BP. Of the mice treated with BP, those which developed tumors soonest had the highest levels of BP antibody. This observation suggested that the antibody to BP may stimulate tumor development. When rabbit antibody to BP was injected with BP a significantly increased tumor formation occurred. Active immunization using BP conjugated to a foreign protein also significantly increased tumor formation when the mice were treated with BP. Our findings suggest that the immune response to carcinogens is an important component of the carcinogenic process.

Benzo[a]pyrene antibody inhibition of benzo[a]pyrene-induced mutagenesis

Summary An antibody to benzo[ a ]pyrene (BP) was prepared. The isolated antibody showed a specificity for BP and a low reactivity with another carcinogenic hydrocarbon, 7,12-dimethylbenz[ a ] anthracene (DMBA). The BP-antibody inhibited the in vitro cytotoxic and mutagenic activity of BP in both a rat embryo fibroblast- and a rat lung cell-mediated mutagenesis system. A possible correlation of these in vitro findings to the in vivo carcinogenesis situation is discussed.

Skin allograft survival and lowered maternal immunologic reactivity

Rejection of skin allografts in mice was delayed from an average of 10.5 days to 13.1 days by daily intraperitoneal injections of cortisone, and to 16.2 days by cortisone plus human chorionic gonadotropin. Placental extract administration resulted in a slightly, but not significantly, increased graft survival. HCG alone, and in combination with other steroids, was ineffective.

Chemical induction of ovarian epithelial carcinoma in mice

Murine ovaries were treated with silk sutures saturated with a solution of 7,12-dimethylbenz(a)anthracene in beeswax. One of 35 animals developed an epithelial carcinoma. This tumor was not successfully transplanted into young animals.

Initiation-promotion skin carcinogenesis and immunological competence.

Summary The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.

Adenylate cyclase stimulation by trypsin.

Summary Adenylate cyclase activity of a rat embryo fibroblast cell line (F111) is markedly increased by brief treatment with 1:300 trypsin. The degree of stimulation depends upon the length of time the cells are treated and the concentration of trypsin. Crystalline trypsin produced a stimulation similar to that obtained with 1:300 trypsin. Further, the addition of soybean trypsin inhibitor blocked the stimulation of adenylate cyclase by 1:300 trypsin. Trypsin-treated adenylate cyclase responds to PGE1, but there is no increase over that of untreated enzyme. This result and the increase in fluoride-stimulated levels of activity suggest that the trypsin is acting upon the catalytic unit of the enzyme.

Sperm-agglutinating and -immobilizing antibody formation following vasectomy prevented with dexamethasone in cynomolgus monkeys*

Cynomolgus monkeys (Macaca fascicularis) were treated with 1.5 mg/kg dexamethasone (DEX) before (4 to 2 days) and after (0, 2, 4, and 7 days) vasectomy. Of the four monkeys treated with DEX, only one developed sperm antibody as measured by sperm-agglutinating and sperm-immobilizing assays. All six of the vasectomized monkeys not given DEX developed both agglutinating and immobilizing sperm antibodies. In this study, DEX given before and after vasectomy blocked sperm-agglutinating and -immobilizing antibody formation. We conclude that the major antigenic exposure to sperm responsible for sperm-agglutinating and -immobilizing antibody comes at the time of vasectomy.

Tumor promotion by foreign bodies (IUD)

Abstract Commercial intrauterine devices (IUDs) were cut into small fragments and implanted subcutaneously and intraperitoneally in mice initiated with 7,12-dimethylbenzanthracene (DMBA). The mice given intraperitoneal IUDs developed significantly more tumors in a shorter time than mice without the IUD. It is suggested that foreign bodies such as the IUD can promote tumors, even at a distance by a humoral mechanism such as autoantibody.

Prevention of monkey sperm penetration of zona-free hamster ova by sperm antibody obtained from vasectomized cynomolgus monkeys*

Incubation of antisperm sera from vasectomized cynomolgus monkeys (Macaca fascicularis) with monkey sperm caused a fourfold reduction of sperm attachment to and penetration of zona-free Golden hamster ova. The attachment of sperm to hamster ova was reduced from 64% to 11%, and the penetration of ova was reduced from 20% to 5%. Sperm antibodies block sperm attachment to the vitelline membrane, thus preventing ovum penetration. This blockage may be one of the reasons for low fertility rates observed following reanastomosis of the vas deferens in those vasectomized males that show high levels of circulating antisperm antibody.

Autoantibody and Tumor Promotion

Summary Following treatment of Strain A mice with either croton oil or TPA, autoantibodies were detected by passive hemagglutination in the sera of the mice. Autoantibody to skin was induced in Strain A mice by the repeated injection of syngeneic skin and liver. Higher levels of antibody were achieved by injection of xenogeneic skin. Mice initiated with DMBA were injected with syngeneic liver and skin. The injected mice developed significantly higher levels of tumors than did noninjected controls. Xenogeneic skin injections produced high levels of autoantibody but did not promote tumor development. The results suggest that autoantibody may play a role in the promotion of tumors.