Detection of mutations in bacteria and of DNA damage and amplified DNA sequences in mammalian cells as a systematic test strategy for elucidating biological activities of chemical carcinogens

Assay‐specific genotoxicity of N‐nitrosodibenzylamine to the rat liver in vivo

“…The differences in the magnitude of the responses observed in the repeat pre-incubation assays in strain TAlOO are unusual in general, but the mutagenicity of nitrosamines is among the most problematical to demonstrate [Muller et al, 19801. The present data confirm the positive results reported by Pool et al [1986] using high S9 levels. The negative data shown here for some of the low S9 experiments probably explains the negative data reported earher by McCann et al [1975] and Jacobson et al [1979].…”

“…The present data also confirm that NDBzA is mutagenic to Salmonella. The two earlier negative reponses recorded in the Salmotiella assay [Jacobson et al, 1979;McCann et al, 1975;Kier et al, 19861 employed the plate incorporation assay protocol and low levels of S9 fraction in the S9 mix, but the positive response reported by Pool et al [1986] used a pre-incubation test and high levels of S9 fraction (30% and "The viabilities of hepatocyte !suspensions isolated from treated rats wJere rrmnitored using the trypan blue exclusion assay. Each of the 4 experiments was accompanied by a negative control animal, and in all experiments NDBzA gave a positive response.…”

Assay‐specific genotoxicity of N‐nitrosodibenzylamine to the rat liver in vivo

“…The differences in the magnitude of the responses observed in the repeat pre-incubation assays in strain TAlOO are unusual in general, but the mutagenicity of nitrosamines is among the most problematical to demonstrate [Muller et al, 19801. The present data confirm the positive results reported by Pool et al [1986] using high S9 levels. The negative data shown here for some of the low S9 experiments probably explains the negative data reported earher by McCann et al [1975] and Jacobson et al [1979].…”

“…The present data also confirm that NDBzA is mutagenic to Salmonella. The two earlier negative reponses recorded in the Salmotiella assay [Jacobson et al, 1979;McCann et al, 1975;Kier et al, 19861 employed the plate incorporation assay protocol and low levels of S9 fraction in the S9 mix, but the positive response reported by Pool et al [1986] used a pre-incubation test and high levels of S9 fraction (30% and "The viabilities of hepatocyte !suspensions isolated from treated rats wJere rrmnitored using the trypan blue exclusion assay. Each of the 4 experiments was accompanied by a negative control animal, and in all experiments NDBzA gave a positive response.…”

Nitrosamine Formation in Processed Hams as Related to Reformulated Elastic Rubber Netting

“…As for NDBzA, the carcinogenicity studies have been limited; NDBzA was reported to be noncarcinogenic in rats (Druckrey et al, 1967). However, other investigations showed this nitrosamine was mutagenic by the Ames Salmonella assay (Pool et al, 1986) and genotoxic in mammalian assays (Boyes et al, 1990;Schmerzer et al, 1990;Brendler et al, 1992) suggesting NDBzA may be a weak carcinogen. Schmerzer et al (1990) postulated a mechanism for the formation of a benzylating species, consistent with the carcinogenicity exhibited by N-nitrosobenzylurea (Ivankovic, 1978) and other nitrosamines containing the benzyl group.…”

Anticancer activity of bisphosphonic acids in methylnitrosourea-induced mammary carcinoma of the rat — benefit of combining bisphosphonates with cytostatic agents

“…Accordingly, we monitored this parameter of genotoxicity in the CO60 cell line used as indicator for DNA amplification. This test was of importance to ensure comparability between the DNA single strand break/hepatocyte and the DNA amplification assay [16]. It was found that 39, 78, 155 and 310 #g APD yielded C-T values of only 3.7, -0.6, 0.6, and 1.8 (for description see legend of Table 5).…”

“…Other specifics of the protocol are indicated in the Results sections. For detection of DNA damage, primary hepatocytes were isolated according to Bradley, Sina and Romruen [21,29,30] and the DNA single strand breaks were analyzed with the method of alkaline elution [16,21,31,32].…”

Assay‐specific genotoxicity of N‐nitrosodibenzylamine to the rat liver in vivo

“…The differences in the magnitude of the responses observed in the repeat pre-incubation assays in strain TAlOO are unusual in general, but the mutagenicity of nitrosamines is among the most problematical to demonstrate [Muller et al, 19801. The present data confirm the positive results reported by Pool et al [1986] using high S9 levels. The negative data shown here for some of the low S9 experiments probably explains the negative data reported earher by McCann et al [1975] and Jacobson et al [1979].…”

“…The present data also confirm that NDBzA is mutagenic to Salmonella. The two earlier negative reponses recorded in the Salmotiella assay [Jacobson et al, 1979;McCann et al, 1975;Kier et al, 19861 employed the plate incorporation assay protocol and low levels of S9 fraction in the S9 mix, but the positive response reported by Pool et al [1986] used a pre-incubation test and high levels of S9 fraction (30% and "The viabilities of hepatocyte !suspensions isolated from treated rats wJere rrmnitored using the trypan blue exclusion assay. Each of the 4 experiments was accompanied by a negative control animal, and in all experiments NDBzA gave a positive response.…”

Nitrosamine Formation in Processed Hams as Related to Reformulated Elastic Rubber Netting

“…As for NDBzA, the carcinogenicity studies have been limited; NDBzA was reported to be noncarcinogenic in rats (Druckrey et al, 1967). However, other investigations showed this nitrosamine was mutagenic by the Ames Salmonella assay (Pool et al, 1986) and genotoxic in mammalian assays (Boyes et al, 1990;Schmerzer et al, 1990;Brendler et al, 1992) suggesting NDBzA may be a weak carcinogen. Schmerzer et al (1990) postulated a mechanism for the formation of a benzylating species, consistent with the carcinogenicity exhibited by N-nitrosobenzylurea (Ivankovic, 1978) and other nitrosamines containing the benzyl group.…”

Anticancer activity of bisphosphonic acids in methylnitrosourea-induced mammary carcinoma of the rat — benefit of combining bisphosphonates with cytostatic agents

“…Accordingly, we monitored this parameter of genotoxicity in the CO60 cell line used as indicator for DNA amplification. This test was of importance to ensure comparability between the DNA single strand break/hepatocyte and the DNA amplification assay [16]. It was found that 39, 78, 155 and 310 #g APD yielded C-T values of only 3.7, -0.6, 0.6, and 1.8 (for description see legend of Table 5).…”

“…Other specifics of the protocol are indicated in the Results sections. For detection of DNA damage, primary hepatocytes were isolated according to Bradley, Sina and Romruen [21,29,30] and the DNA single strand breaks were analyzed with the method of alkaline elution [16,21,31,32].…”

Assay‐specific genotoxicity of N‐nitrosodibenzylamine to the rat liver in vivo

“…The differences in the magnitude of the responses observed in the repeat pre-incubation assays in strain TAlOO are unusual in general, but the mutagenicity of nitrosamines is among the most problematical to demonstrate [Muller et al, 19801. The present data confirm the positive results reported by Pool et al [1986] using high S9 levels. The negative data shown here for some of the low S9 experiments probably explains the negative data reported earher by McCann et al [1975] and Jacobson et al [1979].…”

“…The present data also confirm that NDBzA is mutagenic to Salmonella. The two earlier negative reponses recorded in the Salmotiella assay [Jacobson et al, 1979;McCann et al, 1975;Kier et al, 19861 employed the plate incorporation assay protocol and low levels of S9 fraction in the S9 mix, but the positive response reported by Pool et al [1986] used a pre-incubation test and high levels of S9 fraction (30% and "The viabilities of hepatocyte !suspensions isolated from treated rats wJere rrmnitored using the trypan blue exclusion assay. Each of the 4 experiments was accompanied by a negative control animal, and in all experiments NDBzA gave a positive response.…”

Nitrosamine Formation in Processed Hams as Related to Reformulated Elastic Rubber Netting

“…As for NDBzA, the carcinogenicity studies have been limited; NDBzA was reported to be noncarcinogenic in rats (Druckrey et al, 1967). However, other investigations showed this nitrosamine was mutagenic by the Ames Salmonella assay (Pool et al, 1986) and genotoxic in mammalian assays (Boyes et al, 1990;Schmerzer et al, 1990;Brendler et al, 1992) suggesting NDBzA may be a weak carcinogen. Schmerzer et al (1990) postulated a mechanism for the formation of a benzylating species, consistent with the carcinogenicity exhibited by N-nitrosobenzylurea (Ivankovic, 1978) and other nitrosamines containing the benzyl group.…”

Anticancer activity of bisphosphonic acids in methylnitrosourea-induced mammary carcinoma of the rat — benefit of combining bisphosphonates with cytostatic agents

“…Accordingly, we monitored this parameter of genotoxicity in the CO60 cell line used as indicator for DNA amplification. This test was of importance to ensure comparability between the DNA single strand break/hepatocyte and the DNA amplification assay [16]. It was found that 39, 78, 155 and 310 #g APD yielded C-T values of only 3.7, -0.6, 0.6, and 1.8 (for description see legend of Table 5).…”

“…Other specifics of the protocol are indicated in the Results sections. For detection of DNA damage, primary hepatocytes were isolated according to Bradley, Sina and Romruen [21,29,30] and the DNA single strand breaks were analyzed with the method of alkaline elution [16,21,31,32].…”