Radioprotection by 16,16 dimethyl prostaglandin E2 is equally effective in male and female mice.

Pretreatment with 16,16 dimethyl prostaglandin E2 (DiPGE2) provides effective protection against radiation and chemical injury. Cytoprotection against chemical injury is known to be influenced by sex factors, and is more effective in females than males. Since prostaglandin metabolism and biological responses to prostaglandin may vary between sexes, studies were conducted to compare DiPGE2-induced radioprotection in male and female mice. Pretreatment with 400 micrograms DiPGE2/kg body wt substantially enhanced 30-day survival in males and females. There was no significant difference in the LD50/30 of male and female mice receiving vehicle alone prior to irradiation, 8.34 Gy versus 8.46 Gy, respectively. DiPGE2 treatment increased the LD50/30 in males to 12.1 Gy, providing a dose modification factor (DMF) of 1.45. Similar increases were observed in females, with a LD50/30 of 11.6 and a DMF of 1.37. The reported difference in DiPGE2-induced cytoprotection between males and females exposed to ethanol injury, and the lack of variation in the present radioprotection study suggests that separate mechanisms are involved in two processes.

Proteinuria of B700, a 67 kD albumin-like melanoma-specific antigen.

B700 is a murine melanoma antigen that is closely related to, but distinct from, serum albumin. The present study examined the metabolic fate and anatomic distribution of radioiodinated B700 and mouse serum albumin (MSA) administered s.c. to mice. In blood, both proteins were associated with the plasma fraction where the halflife of B700, a glycoprotein, was 0.5 days, compared to 2.7 days for MSA. Of particular interest was the observation that B700, a 67 kD anionic protein, was excreted primarily in urine. The selective B700-proteinuria did not alter urinary volumes or produce hematuria or edema. SDS-polyacrylamide gel electrophoresis and western blot analysis using the H-2-3-3 B700-specific monoclonal antibody revealed that B700 proteinuria occurred in B-16 murine melanoma bearing animals but not in control mice. These studies demonstrate that the tumor-bearing host readily distinguishes between very similar normal protein (MSA) and tumor-associated antigen (B700) molecules and processes them differently.

B700, an albumin-like melanoma-specific antigen, is a vitamin D binding protein.

B700, a murine melanoma-specific antigen, is a member of the serum albumin protein family. Other members include serum albumin and vitamin D binding protein. The primary structure and biochemical functions of B700, as well as its in vivo metabolic fate, are largely unknown. We compared murine albumin, vitamin D binding protein and B700 for their ability to specifically bind [3H]-1,25-dihydroxy-vitamin D3. Scatchard analysis revealed a single binding site for B700 with a Ka of 51,000 mol/l and a Bmax of 4.51 x 10(-7) mol/l. There was no significant difference in the Ka and Bmax among the albuminoid proteins. However, differences in the binding sites could be distinguished by competition experiments where vitamin D3, vitamin D2 or 7-dehydrocholesterol competed for the specific binding of 1.25-dihydroxyvitamin D3 to a greater extent by B700 than by vitamin D binding protein. The albumin binding site more closely resembles vitamin D binding protein than B700, but the data indicate that the binding function of the albuminoid proteins is conserved in B700.

Comparison of the metabolic fate and tissue distribution of B700, an albumin-like melanoma-specific antigen with serum albumin in normal and tumor-bearing mice.

1. B700, a murine melanoma antigen, is a member of the serum albumin protein family, being closely related to murine serum albumin (MSA). 2. We have studied and compared the metabolic fate and anatomic distribution of radioiodinated B700 and MSA administered to semisyngeneic naive and tumor-bearing mice. 3. Labelled material from both proteins is excreted primarily into urine. 4. The rate of excretion of the two proteins is markedly different, with B700 having a shorter half-life in the body. 5. Despite their similar molecular weights, intact B700 represents approx. 30% of the radioactivity in the urine but only 4% of the MSA in the urine is intact. 6. These studies demonstrate that the host can readily distinguish between very similar normal (MSA) and tumor-associated (B700) molecules and process them differently. 7. Similar findings of differential fate and distribution have been reported in comparing other albuminoid molecules [Dueland S., Blomhoff R. and Pedersen J. I. (1990) Biochem. J. 267, 721-725].

B700, a melanoma-specific antigen, catalyzes metabolism of prostaglandin E2.

B700 is an albumin-like mouse-melanoma-specific antigen of unknown primary structure and biochemical function. The ability of mouse serum albumin to catalyze weak degradation of prostaglandin E2 has been utilized to compare functional similarities between B700 and mouse serum albumin. Both proteins catalyze the degradation of prostaglandin E2 to prostaglandin A2 and prostaglandin B2. This catalytic ability is related to the amino acid composition of the two proteins within the functional region rather than the 3-dimensional configuration, the activity is not altered upon boiling. The primary prostaglandin E2 metabolite in the presence of mouse serum albumin is prostaglandin B2, while prostaglandin A2 predominates in B700 catalyzed degradations. An additional product, presently unidentified, is produced during B700 catalyzed degradation of prostaglandin E2. Our studies indicate that the B700 protein has weak enzymatic activity for prostaglandin E2 similar to that of albumin. To our knowledge, B700 is the only melanoma antigen for which enzymatic activity has been demonstrated.