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β induction by crystalline cadmium sulfide
ENVIRONMENTAL RESEARCH 42, 196-200 (1987)
Inhibition of Interferon-odl3 Induction by Crystalline Cadmium Sulfide GERALD SONNENFELD 1 AND ANDREA M. ROSE
Department of Microbiology and hnmunology and Department of Oral Biology, Schools of Medicine and Dentistry, University of Louisville, Louisville, Kentucky 40292 Received N o v e m b e r 18, 1985 The induction of interferon-call3 by N e w c a s t l e disease virus in L-929 cells was inhibited by p r e t r e a t m e n t of the cell cultures with the crystalline form of c a d m i u m sulfide. As little as 10 ~xg/ml of crystalline c a d m i u m sulfide was sufficient to inhibit the induction of interferon. Cell viability was not affected by this t r e a t m e n t as m e a s u r e d by trypan blue dye-exclusion viability staining. B e t w e e n 6 and 24 hr of preincubation with crystalline c a d m i u m sulfide was required for significant inhibition of interferon induction. © 1987AcademicPress. Inc.
INTRODUCTION Interferon induction has been shown to be inhibited by pretreatment of cell cultures with several different types of carcinogens. Treatment of the cell cultures with closely matched structural analogs that were weakly or noncarcinogenic did not inhibit interferon induction (DeMaeyer and DeMaeyer-Guignard, 1964, 1967; DeMaeyer-Guignard and DeMaeyer, 1965; Hahon et al., 1979; Barnes et al., 1981, Sonnenfeld et al., 1980, 1983a). In addition, several studies have shown that some inorganic metals with possibly carcinogenic activities can also inhibit interferon-~/[3 induction (Treagen and Furst, 1970; Pribyl and Treagen, 1977; Hahon et al., 1980; Hahon and Booth, 1984). Pretreatment of cell cultures with nickel, chromium, or manganese severely inhibited interferon induction, while treatment of the cultures with cadmium had no effect. This lead Pribyl and Treagen (1977) to hypothesiie that inhibition of interferon production by metals did not necessarily correlate with potential carcinogenic activity. We have recently shown that the structural form of nickel played a major role in determining whether the nickel could inhibit interferon induction (Sonnenfeld et al., 1983b). Pretreatment of cell cultures with crystalline nickel sulfide, which has some reported carcinogenic effects in epidemiological and other studies, inhibited interferon-od[3 production. Treatment of the cell cultures with amorphous nickel sulfide, which has no reported carcinogenic effects, did not inhibit interferon induction (Sonnenfeld et al., 1983b). The present study was carried out to determine if the structural form of cadmium could also affect the ability of cadmium to inhibit interferon-od[3 induction. t To w h o m r e q u e s t s for reprints should be addressed.
196 0013-9351/87 $3.00 Copyright © 1987by Academic Press, Inc. All rights of reproduction in any form reserved.
CdS AND INTERFERON
197
MATERIALS AND METHODS
Mouse tissue culture. Mouse L-929 cells, originally obtained from the American Type Culture Collection, Rockville, Maryland, were maintained in our laboratory in minimum essential medium (GIBCO Laboratories, Grand Island, N.Y.) supplemented with antibiotics, L-glutamine, and 10% fetal bovine serum (Golemboski and Sonnenfeld, 1984). Metals. Crystalline cadmium sulfide was purchased from Alfa Inorganics, Danvers, Massachusetts, and was suspended in minimum essential medium at the appropriate concentration prior to use. It was made by high temperature synthesis techniques and exhibited crystalline properties based upon X-ray diffraction studies. Treatment of culture with metals. The mouse L-929 cells were grown to confluent monolayers of approximately 5 x 10 6 cells, and then treated with various concentrations of crystalline cadmium sulfide. After the appropriate incubation period in 5% CO2 at 37°C, the cells were sequentially washed with minimum essential medium containing 10% fetal bovine serum and then with minimum essential medium without serum. Interferon-alpha/beta was then induced, and 24 hr later culture supernatant fluids were removed and assayed for interferon activity. Experimental treatment resulting in inhibition of interferon production was considered to have occurred when the interferon titer was reduced by 50% or more in a statistically significant fashion compared to controls (Barnes et al., 1981). Cell viability was determined by means of the trypan blue dye exclusion procedure at the time that supernatant fluids were harvested from the cells. Induction of interferon-od#. Murine interferon-call3 was induced with the Herts strain of Newcastle disease virus as described elsewhere (Hanna et al., 1966). Residual virus was inactivated by pH 2 treatment of supernatant fluids for 5 days at 4°C prior to assay. Interferon type was identified as interferon-alpha/beta by neutralization with antibody (Sonnenfeld et al., 1977). Assay of interferon. Interferon antiviral titers were determined by means of a plaque reduction assay on mouse L-929 cells using the Indiana strain of vesicular stomatitis virus (Hanna et al., 1977). The interferon titer, expressed as units per milliliter, corresponded to the reciprocal of the highest dilution of test sample that reduced virus plaques by 50%. One interferon antiviral unit in this assay was equivalent to 0.88 NIH G-002-904-511 reference units. Statistical analysis. Statistical analysis of the data was carried out by means of Student's t test with oLset a priori at P < 0.05. RESULTS
Dosages of Crystalline Cadmium Sulfide Required for Inhibition of Interferon Induction In this series of experiments, L-929 cells were treated with three different dosages of crystalline cadmium sulfide. After 24 hr of incubation (Sonnenfeld et al., 1983b) the cadmium sulfide was removed, the cells were washed, and interferon-odl3 was induced with Newcastle disease virus. Twenty-four hours later, culture supernatant fluids were removed, the virus was inactivated, and the fluids
198
SONNENFELD AND ROSE TABLE 1 EFFECT OF EXPOSURE OF L-929 CELLS TO CRYSTALLINE CADMIUM SULFIDE FOR 24 HR ON INTERFERON-call3 INDUCTION BY NEWCASTLE DISEASE VIRUS
Treatment
No. of expt.
None 1 Fg CdS 10 ixg CdS 50 fxg CdS
10 8 7 8
Interferon titer _+ S E M a 733 318 226 348
_+ _+ _+ +-
241 82 24 91
P -NS b <0.05 <0.05
SEM, stan dard error of the mean; interferon titer e x p r e s s e d as units/ml. b NS, not significant; P values are c o m p a r e d to untreat e d controls.
were then assayed for interferon-~/[3 activity. Viabilities of all treated and control cultures after virus challenge were greater than 90% and did not significantly vary from each other. As little as 10 txg/ml of crystalline cadmium sulfide was sufficient to inhibit the induction of interferon-a/J3 using this protocol (Table 1).
Time o f Incubation Required for Inhibition of Interferon Induction by Cadmium Sulfide These experiments were carried out using 10 p.g/ml of cadmium sulfide and the time of incubation of cadmium sulfide with the cell cultures was 3 or 6 hr. In this case, viabilities of the cell cultures were all greater than 90% and did not significantly vary from each other at the time of harvest of culture supernatant fluids. These incubation times were not sufficient for crystalline cadmium sulfide to inhibit interferon-a/J3 production by greater than 50% (Table 2).
DISCUSSION Induction of interferon-od[3 in vitro has been shown to be inhibited by treatment of cell cultures with a variety of organic carcinogens, while closely matched structural analogs that were weakly or noncarcinogenic had no effect (DeMaeyer and DeMaeyer-Guignard, 1964, 1967; DeMaeyer-Guignard and DeMaeyer, 1965; Hahon et al., 1979; Barnes et al., 1981; Sonnenfeld et al., 1980, 1983). The treatments with carcinogens had no effect on cell viability and did not inhibit the ability of the virus to replicate in the treated cells. The situation with inorganic metals that may have carcinogenic potential has TABLE 2 EFFECT OF DIFFERENT TIMES OF EXPOSURE OF L-929 CELLS TO 10 ixg/ml CRYSTALLINE CADMIUM SULFIDE ON INHIBITION OF INTERFERON-ed~ INDUCTION BY NEWCASTLE DISEASE VIRUS Time of CdS e x p o s u r e
No. of expt.
None 3 hr None 6 hr
5 4 10 10
Interferon titer S E M a
a SEM, s t a n d a r d error; interferon titer e x p r e s s e d as units/ml. b p values c o m p a r e d to u n t r e a t e d controls; NS, not significant.
547 533 533 392
_+ _+ _+ _+
99 104 52 44
pb -NS -<0.05
CdS AND INTERFERON
199
been less clear. Pretreatment of cell cultures with nickel did result in inhibition of interferon-od[3 production (Treagen and Furst, 1970; H a h o n et al., 1980). However, pretreatment of cell cultures with cadmium produced inconsistent or negative results (Pribyl and Treagen, 1977). Recently, we showed that the structural form of the metal played a role in the ability of nickel to inhibit interferon induction (Sonnenfeld et al., 1983b). Crystalline nickel sulfide inhibited interferon-a/J3 induction, while amorphous nickel sulfide had no effect. Since the earlier experiments with cadmium did not rigorously define the form and dosage of the metal (Pribyl and Treagen, 1977), we decided to determine if the structural form of cadmium can effect its ability to inhibit interferon induction. The results of the present study indicate that pretreatment of cell cultures with crystalline cadmium sulfide for 24 hr can result in inhibition of interferon-od[3 induction. Unfortunately, we could not compare the effects of crystalline cadmium sulfide with those of amorphous cadmium sulfide, because amorphous cadmium sulfide does not appear to be stable, due to the generation of CdSO 4 oxidative products. In any case, inhibition of interferon induction does appear to correlate with carcinogenic potential of cadmium when the appropriate structural form of cadmium, crystalline cadmium sulfide, is used. Treatment of the cell cultures with crystalline cadmium sulfide for less than 24 hr did not result in inhibition of interferon-~/[3 induction according to our definition of inhibition (Barnes et al., 1981). When a polycyclic aromatic carcinogen, benzo[a]pyrene, was used, a 24-hr period of incubation was also required (Golemboski and Sonnenfeld, 1984, 1985). This incubation was required for activation of the benzo[a]pyrene or other organic carcinogen by microsomal enzymes, and could be reduced when preactivated benzo[a]pyrene was added to the cultures ( D e L o r and Sonnenfeld, 1985; Hahon, 1985; Crowe and Sonnenfeld, submitted). Therefore, it was surprising that crystalline cadmium sulfide also required a long incubation period in order to inhibit interferon induction. This may indicate differences in the mechanisms by which organic and inorganic carcinogens inhibit interferon-call3 induction.
ACKNOWLEDGMENTS This study was funded in part by a grant from the Phi Beta Psi sorority. The authors thank Dr. Max Costa of the University of Texas Medical School at Houston for his helpful suggestions and comments. We also thank Ms. Cyndy Eaton for her invaluable technical assistance. REFERENCES Barnes, M. C., Streips, U. N., and Sonnenfeld, G. (1981). Effects of carcinogens and analogs on interferon induction. Oncology 38, 98-101. DeLor, D. K. D., and Sonnenfeld, G. (1985). Studies on activation of benzo[a]pyrene for inhibition of interferon induction. Environ. Res. 37, 205-211. DeMaeyer, E., and DeMaeyer-Guignard, J. (1964). Inhibition by 3-methylcholanthrene of interferon formation in rat embryo cells infected with Sindbis virus. J. Natl. Cancer Inst. 32, 1317-1321. DeMaeyer, E., and DeMaeyer-Guignard, J. (1967). Inhibition of interferon synthesis by triethyleneamine and 4-nitroquinoline-N-oxide.Arch. Gesamte Virusforsch. 22, 61-68. DeMaeyer-Guignard, J., and DeMaeyer, E. (1965). Effect of carcinogenic and non-carcinogenic hydrocarbons on interferon synthesis and virus plaque development. J. Natl. Cancer Inst. 34, 265-276.
200
SONNENFELD AND ROSE
Golemboski, K. A., and Sonnenfeld, G. (1984). Reversibility of inhibition of interferon-alpha/beta induction by benzo[a]pyrene. J. Natl. Cancer Inst. 73,763-766. Golemboski, K. A., and Sonnenfeld, G. (1985). Kinetics of inhibition of in vitro interferon-alpha/beta production after benzo-(a)-pyrene exposure. Oncology 42, 169-173. Hahon, N. (1985). Inhibition of viral interferon induction in mammalian cell cultures by azo dyes and derivatives activated with rat liver $9 fraction. Environ. Res. 37, 228-238. Hahon, N., and Booth, J. A. (1984). Effect of chromium and manganese particles on the interferon system. J. Interferon Res. 4, 17-27. Hahon, N., Booth, J. A., and Pearson, D. J. (1980). Inhibition of viral infection induction in mammalian cell monolayers by metallic copper, aluminum and nickel particles. In "The in Vitro Effects of Mineral Dusts" (R. C. Brown et al., Eds.), pp. 219-228, Academic Press, New York. Hahon, N., Booth, J. A., and Stewart, J. D. (1979). Aflatoxin inhibition of viral interferon induction. Antimicrob. Agents Chemother. 16, 277-282. Hanna, C., Merigan, T. C., and Jawetz, E. (1966). Inhibition of TRIC agents by virus-induced interferon. Proc. Sac. Exp. Biol. Med. 122, 417-422. Pribyl, D., and Treagen, L. (1977). A comparison of the effect of metal carcinogens chromium, cadmium and nickel on the interferon system. Acta Virol. 21, 507. Sonnenfeld, G., Barnes, M. C., Schooler, J., and Streips, U. N. (1980). Inhibition of interferon induction as a screen for the carcinogenic potential of chemicals. In "Interferon: Properties and Clinical Uses" (A. Khan, N. O. Hill, and G. L. Dorn, Eds.), pp. 589-598, Leland Fikes Foundation Press, Dallas. Sonnenfeld, G., Hudgens, R. W., and Streips, U. N. (1983a). Effect of environmental carcinogens and other chemicals on murine alpha/beta interferon production. Environ. Res. 31, 355-361. Sonnenfeld, G., Mandel, A. D., and Merigan, T. C. (1977). The immunosuppressive effect of Type II mouse interferon on antibody production. Cell. Immunol. 34, 193-206. Sonnenfeld, G., Streips, U. N , and Costa, M. (1983b). Differential effects of amorphous and crystalline nickel sulfide on murine alpha/beta interferon production. Environ. Res. 32, 474-479. Treagen, L., and Furst, A. (1970). Inhibition of interferon synthesis in mammalian cell cultures after nickel treatment. Res. Commun. Chem. Pathol. Pharmacol. 1, 395-402.
Inhibition of Interferon-odl3 Induction by Crystalline Cadmium Sulfide GERALD SONNENFELD 1 AND ANDREA M. ROSE
Department of Microbiology and hnmunology and Department of Oral Biology, Schools of Medicine and Dentistry, University of Louisville, Louisville, Kentucky 40292 Received N o v e m b e r 18, 1985 The induction of interferon-call3 by N e w c a s t l e disease virus in L-929 cells was inhibited by p r e t r e a t m e n t of the cell cultures with the crystalline form of c a d m i u m sulfide. As little as 10 ~xg/ml of crystalline c a d m i u m sulfide was sufficient to inhibit the induction of interferon. Cell viability was not affected by this t r e a t m e n t as m e a s u r e d by trypan blue dye-exclusion viability staining. B e t w e e n 6 and 24 hr of preincubation with crystalline c a d m i u m sulfide was required for significant inhibition of interferon induction. © 1987AcademicPress. Inc.
INTRODUCTION Interferon induction has been shown to be inhibited by pretreatment of cell cultures with several different types of carcinogens. Treatment of the cell cultures with closely matched structural analogs that were weakly or noncarcinogenic did not inhibit interferon induction (DeMaeyer and DeMaeyer-Guignard, 1964, 1967; DeMaeyer-Guignard and DeMaeyer, 1965; Hahon et al., 1979; Barnes et al., 1981, Sonnenfeld et al., 1980, 1983a). In addition, several studies have shown that some inorganic metals with possibly carcinogenic activities can also inhibit interferon-~/[3 induction (Treagen and Furst, 1970; Pribyl and Treagen, 1977; Hahon et al., 1980; Hahon and Booth, 1984). Pretreatment of cell cultures with nickel, chromium, or manganese severely inhibited interferon induction, while treatment of the cultures with cadmium had no effect. This lead Pribyl and Treagen (1977) to hypothesiie that inhibition of interferon production by metals did not necessarily correlate with potential carcinogenic activity. We have recently shown that the structural form of nickel played a major role in determining whether the nickel could inhibit interferon induction (Sonnenfeld et al., 1983b). Pretreatment of cell cultures with crystalline nickel sulfide, which has some reported carcinogenic effects in epidemiological and other studies, inhibited interferon-od[3 production. Treatment of the cell cultures with amorphous nickel sulfide, which has no reported carcinogenic effects, did not inhibit interferon induction (Sonnenfeld et al., 1983b). The present study was carried out to determine if the structural form of cadmium could also affect the ability of cadmium to inhibit interferon-od[3 induction. t To w h o m r e q u e s t s for reprints should be addressed.
196 0013-9351/87 $3.00 Copyright © 1987by Academic Press, Inc. All rights of reproduction in any form reserved.
CdS AND INTERFERON
197
MATERIALS AND METHODS
Mouse tissue culture. Mouse L-929 cells, originally obtained from the American Type Culture Collection, Rockville, Maryland, were maintained in our laboratory in minimum essential medium (GIBCO Laboratories, Grand Island, N.Y.) supplemented with antibiotics, L-glutamine, and 10% fetal bovine serum (Golemboski and Sonnenfeld, 1984). Metals. Crystalline cadmium sulfide was purchased from Alfa Inorganics, Danvers, Massachusetts, and was suspended in minimum essential medium at the appropriate concentration prior to use. It was made by high temperature synthesis techniques and exhibited crystalline properties based upon X-ray diffraction studies. Treatment of culture with metals. The mouse L-929 cells were grown to confluent monolayers of approximately 5 x 10 6 cells, and then treated with various concentrations of crystalline cadmium sulfide. After the appropriate incubation period in 5% CO2 at 37°C, the cells were sequentially washed with minimum essential medium containing 10% fetal bovine serum and then with minimum essential medium without serum. Interferon-alpha/beta was then induced, and 24 hr later culture supernatant fluids were removed and assayed for interferon activity. Experimental treatment resulting in inhibition of interferon production was considered to have occurred when the interferon titer was reduced by 50% or more in a statistically significant fashion compared to controls (Barnes et al., 1981). Cell viability was determined by means of the trypan blue dye exclusion procedure at the time that supernatant fluids were harvested from the cells. Induction of interferon-od#. Murine interferon-call3 was induced with the Herts strain of Newcastle disease virus as described elsewhere (Hanna et al., 1966). Residual virus was inactivated by pH 2 treatment of supernatant fluids for 5 days at 4°C prior to assay. Interferon type was identified as interferon-alpha/beta by neutralization with antibody (Sonnenfeld et al., 1977). Assay of interferon. Interferon antiviral titers were determined by means of a plaque reduction assay on mouse L-929 cells using the Indiana strain of vesicular stomatitis virus (Hanna et al., 1977). The interferon titer, expressed as units per milliliter, corresponded to the reciprocal of the highest dilution of test sample that reduced virus plaques by 50%. One interferon antiviral unit in this assay was equivalent to 0.88 NIH G-002-904-511 reference units. Statistical analysis. Statistical analysis of the data was carried out by means of Student's t test with oLset a priori at P < 0.05. RESULTS
Dosages of Crystalline Cadmium Sulfide Required for Inhibition of Interferon Induction In this series of experiments, L-929 cells were treated with three different dosages of crystalline cadmium sulfide. After 24 hr of incubation (Sonnenfeld et al., 1983b) the cadmium sulfide was removed, the cells were washed, and interferon-odl3 was induced with Newcastle disease virus. Twenty-four hours later, culture supernatant fluids were removed, the virus was inactivated, and the fluids
198
SONNENFELD AND ROSE TABLE 1 EFFECT OF EXPOSURE OF L-929 CELLS TO CRYSTALLINE CADMIUM SULFIDE FOR 24 HR ON INTERFERON-call3 INDUCTION BY NEWCASTLE DISEASE VIRUS
Treatment
No. of expt.
None 1 Fg CdS 10 ixg CdS 50 fxg CdS
10 8 7 8
Interferon titer _+ S E M a 733 318 226 348
_+ _+ _+ +-
241 82 24 91
P -NS b <0.05 <0.05
SEM, stan dard error of the mean; interferon titer e x p r e s s e d as units/ml. b NS, not significant; P values are c o m p a r e d to untreat e d controls.
were then assayed for interferon-~/[3 activity. Viabilities of all treated and control cultures after virus challenge were greater than 90% and did not significantly vary from each other. As little as 10 txg/ml of crystalline cadmium sulfide was sufficient to inhibit the induction of interferon-a/J3 using this protocol (Table 1).
Time o f Incubation Required for Inhibition of Interferon Induction by Cadmium Sulfide These experiments were carried out using 10 p.g/ml of cadmium sulfide and the time of incubation of cadmium sulfide with the cell cultures was 3 or 6 hr. In this case, viabilities of the cell cultures were all greater than 90% and did not significantly vary from each other at the time of harvest of culture supernatant fluids. These incubation times were not sufficient for crystalline cadmium sulfide to inhibit interferon-a/J3 production by greater than 50% (Table 2).
DISCUSSION Induction of interferon-od[3 in vitro has been shown to be inhibited by treatment of cell cultures with a variety of organic carcinogens, while closely matched structural analogs that were weakly or noncarcinogenic had no effect (DeMaeyer and DeMaeyer-Guignard, 1964, 1967; DeMaeyer-Guignard and DeMaeyer, 1965; Hahon et al., 1979; Barnes et al., 1981; Sonnenfeld et al., 1980, 1983). The treatments with carcinogens had no effect on cell viability and did not inhibit the ability of the virus to replicate in the treated cells. The situation with inorganic metals that may have carcinogenic potential has TABLE 2 EFFECT OF DIFFERENT TIMES OF EXPOSURE OF L-929 CELLS TO 10 ixg/ml CRYSTALLINE CADMIUM SULFIDE ON INHIBITION OF INTERFERON-ed~ INDUCTION BY NEWCASTLE DISEASE VIRUS Time of CdS e x p o s u r e
No. of expt.
None 3 hr None 6 hr
5 4 10 10
Interferon titer S E M a
a SEM, s t a n d a r d error; interferon titer e x p r e s s e d as units/ml. b p values c o m p a r e d to u n t r e a t e d controls; NS, not significant.
547 533 533 392
_+ _+ _+ _+
99 104 52 44
pb -NS -<0.05
CdS AND INTERFERON
199
been less clear. Pretreatment of cell cultures with nickel did result in inhibition of interferon-od[3 production (Treagen and Furst, 1970; H a h o n et al., 1980). However, pretreatment of cell cultures with cadmium produced inconsistent or negative results (Pribyl and Treagen, 1977). Recently, we showed that the structural form of the metal played a role in the ability of nickel to inhibit interferon induction (Sonnenfeld et al., 1983b). Crystalline nickel sulfide inhibited interferon-a/J3 induction, while amorphous nickel sulfide had no effect. Since the earlier experiments with cadmium did not rigorously define the form and dosage of the metal (Pribyl and Treagen, 1977), we decided to determine if the structural form of cadmium can effect its ability to inhibit interferon induction. The results of the present study indicate that pretreatment of cell cultures with crystalline cadmium sulfide for 24 hr can result in inhibition of interferon-od[3 induction. Unfortunately, we could not compare the effects of crystalline cadmium sulfide with those of amorphous cadmium sulfide, because amorphous cadmium sulfide does not appear to be stable, due to the generation of CdSO 4 oxidative products. In any case, inhibition of interferon induction does appear to correlate with carcinogenic potential of cadmium when the appropriate structural form of cadmium, crystalline cadmium sulfide, is used. Treatment of the cell cultures with crystalline cadmium sulfide for less than 24 hr did not result in inhibition of interferon-~/[3 induction according to our definition of inhibition (Barnes et al., 1981). When a polycyclic aromatic carcinogen, benzo[a]pyrene, was used, a 24-hr period of incubation was also required (Golemboski and Sonnenfeld, 1984, 1985). This incubation was required for activation of the benzo[a]pyrene or other organic carcinogen by microsomal enzymes, and could be reduced when preactivated benzo[a]pyrene was added to the cultures ( D e L o r and Sonnenfeld, 1985; Hahon, 1985; Crowe and Sonnenfeld, submitted). Therefore, it was surprising that crystalline cadmium sulfide also required a long incubation period in order to inhibit interferon induction. This may indicate differences in the mechanisms by which organic and inorganic carcinogens inhibit interferon-call3 induction.
ACKNOWLEDGMENTS This study was funded in part by a grant from the Phi Beta Psi sorority. The authors thank Dr. Max Costa of the University of Texas Medical School at Houston for his helpful suggestions and comments. We also thank Ms. Cyndy Eaton for her invaluable technical assistance. REFERENCES Barnes, M. C., Streips, U. N., and Sonnenfeld, G. (1981). Effects of carcinogens and analogs on interferon induction. Oncology 38, 98-101. DeLor, D. K. D., and Sonnenfeld, G. (1985). Studies on activation of benzo[a]pyrene for inhibition of interferon induction. Environ. Res. 37, 205-211. DeMaeyer, E., and DeMaeyer-Guignard, J. (1964). Inhibition by 3-methylcholanthrene of interferon formation in rat embryo cells infected with Sindbis virus. J. Natl. Cancer Inst. 32, 1317-1321. DeMaeyer, E., and DeMaeyer-Guignard, J. (1967). Inhibition of interferon synthesis by triethyleneamine and 4-nitroquinoline-N-oxide.Arch. Gesamte Virusforsch. 22, 61-68. DeMaeyer-Guignard, J., and DeMaeyer, E. (1965). Effect of carcinogenic and non-carcinogenic hydrocarbons on interferon synthesis and virus plaque development. J. Natl. Cancer Inst. 34, 265-276.
200
SONNENFELD AND ROSE
Golemboski, K. A., and Sonnenfeld, G. (1984). Reversibility of inhibition of interferon-alpha/beta induction by benzo[a]pyrene. J. Natl. Cancer Inst. 73,763-766. Golemboski, K. A., and Sonnenfeld, G. (1985). Kinetics of inhibition of in vitro interferon-alpha/beta production after benzo-(a)-pyrene exposure. Oncology 42, 169-173. Hahon, N. (1985). Inhibition of viral interferon induction in mammalian cell cultures by azo dyes and derivatives activated with rat liver $9 fraction. Environ. Res. 37, 228-238. Hahon, N., and Booth, J. A. (1984). Effect of chromium and manganese particles on the interferon system. J. Interferon Res. 4, 17-27. Hahon, N., Booth, J. A., and Pearson, D. J. (1980). Inhibition of viral infection induction in mammalian cell monolayers by metallic copper, aluminum and nickel particles. In "The in Vitro Effects of Mineral Dusts" (R. C. Brown et al., Eds.), pp. 219-228, Academic Press, New York. Hahon, N., Booth, J. A., and Stewart, J. D. (1979). Aflatoxin inhibition of viral interferon induction. Antimicrob. Agents Chemother. 16, 277-282. Hanna, C., Merigan, T. C., and Jawetz, E. (1966). Inhibition of TRIC agents by virus-induced interferon. Proc. Sac. Exp. Biol. Med. 122, 417-422. Pribyl, D., and Treagen, L. (1977). A comparison of the effect of metal carcinogens chromium, cadmium and nickel on the interferon system. Acta Virol. 21, 507. Sonnenfeld, G., Barnes, M. C., Schooler, J., and Streips, U. N. (1980). Inhibition of interferon induction as a screen for the carcinogenic potential of chemicals. In "Interferon: Properties and Clinical Uses" (A. Khan, N. O. Hill, and G. L. Dorn, Eds.), pp. 589-598, Leland Fikes Foundation Press, Dallas. Sonnenfeld, G., Hudgens, R. W., and Streips, U. N. (1983a). Effect of environmental carcinogens and other chemicals on murine alpha/beta interferon production. Environ. Res. 31, 355-361. Sonnenfeld, G., Mandel, A. D., and Merigan, T. C. (1977). The immunosuppressive effect of Type II mouse interferon on antibody production. Cell. Immunol. 34, 193-206. Sonnenfeld, G., Streips, U. N , and Costa, M. (1983b). Differential effects of amorphous and crystalline nickel sulfide on murine alpha/beta interferon production. Environ. Res. 32, 474-479. Treagen, L., and Furst, A. (1970). Inhibition of interferon synthesis in mammalian cell cultures after nickel treatment. Res. Commun. Chem. Pathol. Pharmacol. 1, 395-402.