Radioimmunoassays specific for the N and C termini of human prothymosin a and the N terminus of human parathymosin a were employed for the measurement of the levels of a-thymosins in human thymus, spleen, and liver during normal growth and intestine and breast in malignant growth. A differential expression of the two a-thymosins was observed in thymus (prothymosin a-rich) and liver (parathymosin a-rich). A decline in the levels of both a-thymosins was found with age, with prothymosin a in thymus showing the sharpest change (15-to 30-fold). The levels of both a-thymosins were higher in malignant tissues as compared with healthy ones. In breast cancer, in particular, the mean increase for prothymosin a and parathymosin a was 17.9-and 11.5-fold, respectively. The major crossreactive material was characterized in all cases as intact prothymosin a and parathymosin a. These results suggest an in vivo relationship of the expression of a-thymosins with the human tissue cell proliferation activity.Human prothymosin a (1) and parathymosin a (2) are 109 and 101 residues long and partly homologous, particularly at their N termini. They are ubiquitous in mammalian tissues (1, 3).Existing literature for the two a-thymosins points toward an extracellular role of immunologic nature and an intracellular role related to cell growth. In the immunologic direction, thymosin al (the N-terminal fragment 1-28 of prothymosin a) and/or prothymosin a have been reported to increase the expression of interleukin 2 (IL-2) and IL-2 high-affinity receptors in normal human lymphocytes (4,5), cooperate with a,B-interferon in boosting natural killer (NK) activity in immunosuppressed and tumor-bearing mice (6), and restore deficient autologous and allogeneic mixed lymphocyte responses in lymphocytes from patients with clinically active multiple sclerosis (7) and systemic lupus erythematosus (8). In cell growth, increased levels of mRNA for prothymosin a have been observed in lymphocytes stimulated with mitogens and serum reconstitution (1, 9), in lymphocytes of leukemic patients (10), and in regenerating liver (9). The activation of the protooncogene MYC was also reported to lead to rapid increase in transcription of the prothymosin a gene (11), and antisense oligomers for prothymosin a were found to inhibit myeloma cell division (12). J.G. and Ch.M.) from breast and (by D.P.) from colon cancer patients. Tissues were stored at -45°C. Extraction was carried out according to Tsitsiloni et al. (13). MATERIALS AND METHODSThe radioimmunoassay for the N terminus of prothymosin a was carried out as described by Yialouris et al. (14). The radioimmunoassays for the C terminus of prothymosin a and the N terminus of parathymosin a were developed by generating rabbit antisera against the synthetic peptides human prothymosin-a-(90-109) and human parathymosin-a-(1-30), both with an N-terminal extension of Cys-Aca (Aca, aminocaproic acid) and coupled to keyhole limpet hemocyanin (KLH). The synthetic peptides human prothymosin-a-(90-109) and human parathy...

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The metallothionein (MT) family is a class of low molecular weight, intracellular and cysteine-rich proteins presenting high affinity for metal ions. Although the members of this family were discovered nearly 40 years ago, their functional significance remains obscure. Four major MT isoforms, MT-1, MT-2, MT-3 and MT-4, have been identified in mammals. MTs are involved in many pathophysiological processes such as metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, chemoresistance and radiotherapy resistance. MT isoforms have been shown to be involved in several aspects of the carcinogenic process, cancer development and progression. MT expression has been implicated as a transient response to any form of stress or injury providing cytoprotective action. Although MT participates in the carcinogenic process, its use as a potential marker of tumor differentiation or cell proliferation, or as a predictor of poor prognosis remains unclear. In the present review the involvement of MT in defense mechanisms to toxicity and in carcinogenicity is discussed.

The metallothionein (MT) family is a class of low molecular weight, intracellular and cysteine-rich proteins presenting high affinity for metal ions. Although the members of this family were discovered nearly 40 years ago, their functional significance remains obscure. Four major MT isoforms, MT-1, MT-2, MT-3 and MT-4, have been identified in mammals. MTs are involved in many pathophysiological processes such as metal ion homeostasis and detoxification, protection against oxidative damage, cell proliferation and apoptosis, chemoresistance and radiotherapy resistance. MT isoforms have been shown to be involved in several aspects of the carcinogenic process, cancer development and progression. MT expression has been implicated as a transient response to any form of stress or injury providing cytoprotective action. Although MT participates in the carcinogenic process, its use as a potential marker of tumor differentiation or cell proliferation, or as a predictor of poor prognosis remains unclear. In the present review the involvement of MT in defense mechanisms to toxicity and in carcinogenicity is discussed.

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