methylnitronitrosoguanidine and Lymphoma--Non-Hodgkin

A small fraction of those individuals exposed to cytotoxic chemotherapy or radiation for the treatment of a primary malignant disease will develop a second malignancy some time later. Although exposure to the cytotoxic agents is believed to be the causative factor, the reason only certain individuals develop the second malignancy is unknown. Some studies have suggested that these individuals might be predisposed to cancer because of an inherent sensitivity to the alkylating agents used in cancer therapy. We have reported that these individuals with therapy-related acute nonlymphocytic leukemia (t-ANLL) have reduced endogenous levels of the repair protein O6-alkylguanine alkyltransferase (AGT). To further investigate the etiology of this disease, alkylation-induced sister-chromatid exchange (SCE) formation in individuals who developed second malignancies, was compared to other patient groups and normal controls. Peripheral blood lymphocytes from patients with (1) t-ANLL, (2) primary forms of acute nonlymphocytic leukemia (ANLL de novo), (3) patients with primary malignancies at risk of developing secondary disease, and (4) unexposed, healthy controls were treated in vitro with N-methyl-N'-nitro-nitrosoguanidine or mitomycin C. Baseline and mutagen-induced frequencies of SCEs were determined. These studies failed to detect any increased sensitivity in those patients who developed second malignancies as compared to controls or patients with de novo forms of the same disease. Also, no correlation between sensitivity to the alkylating agent N-methyl-N'-nitro-nitrosoguanidine and endogenous levels of the AGT repair protein was found. These results suggest that t-ANLL patients are not sensitive to SCE induction by either MNNG or MMC.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Agents; DNA Replication; Hodgkin Disease; Humans; Leukemia, Myeloid, Acute; Lymphocytes; Lymphoma, Non-Hodgkin; Male; Methylnitronitrosoguanidine; Methyltransferases; Mitomycin; Mitomycins; O(6)-Methylguanine-DNA Methyltransferase; Sister Chromatid Exchange

The frequency and distribution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced structural aberrations, i.e., chromatid and chromosome gaps, breaks, and exchanges, were studied in fibroblasts from 16 patients with sarcoma, 15 with non-Hodgkin's lymphoma (NHL), and 14 controls. The mean frequencies of aberrant cells, and gap, break, and gap + break events per 100 cells were 22.9, 5.1, 28.6, and 33.7 in the sarcoma group; 19.1, 5.0, 22.5, and 27.5 in the NHL group; and 23.5, 6.1, 33.5, and 39.6 in the control group. None of the differences between the groups were statistically significant. The distribution of MNNG-induced aberrations was non-random (P less than 0.001) in all 3 groups. Eight, 11, and 17 chromosome bands in the sarcoma, NHL, and control groups, respectively, were particularly break-prone. Only 2 hot spots in the sarcoma group (1p32, 11q23), and 3 in the NHL group (1p36, 3q25, 6p21), coincided with the 25 and 60 bands known to be involved in primary rearrangements in sarcomas and NHL. We conclude that neither the frequency nor the distribution of MNNG-induced chromosomal aberrations indicates any latent chromosomal instability in sarcoma and NHL patients.

Topics: Chromosome Aberrations; Chromosome Banding; Chromosome Mapping; Chromosomes; DNA Damage; Female; Humans; Lymphoma, Non-Hodgkin; Male; Methylnitronitrosoguanidine; Sarcoma

Of 158 channel catfish (Ictalurus punctatus) exposed to N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS:70-25-7] in water for 28 days, 2 developed disseminated lymphosarcoma. One fish was necropsied at 12 months and another at 18 months following exposure. Both fish had a massive neoplastic infiltration of the bilateral pairs of head and trunk kidneys from which the neoplastic cells appeared to originate. The neoplastic infiltration was also observed in the following: thymus, gills, oral mucosa, liver, skin, skeletal muscle of head-neck region, and to a lesser extent spleen and bone marrow. This is probably the first report of lymphosarcoma in channel catfish. Although the occurrence of lymphosarcoma in these 2 catfish appeared to be related to exposure to MNNG, the exact role MNNG played in the tumor formation was not determined.

Topics: Animals; Carcinoma; Carcinoma, Squamous Cell; Fish Diseases; Fishes; Kidney Neoplasms; Lipoma; Lymphoma, Non-Hodgkin; Methylnitronitrosoguanidine; Mouth Mucosa; Mouth Neoplasms; Papilloma; Water Pollutants, Chemical