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Induction of different genetic changes by different classes of chemical carcinogens during progression of mouse skin tumors
Author(s) -
Bremner Rod,
Kemp Christopher J.,
Balmain Allan
Publication year - 1994
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940110206
Subject(s) - biology , carcinogen , genetics , cancer research
Abstract By analysis of skin tumors from F 1 hybrid mice we demonstrated that the genetic events that occur during tumor progression depend on the type of chemical carcinogenesis protocol used to induce tumor growth. More than 95% of tumors induced by initiation with 7, 12‐dimethylbenz[ a ]anthracene (DMBA) and promotion with 12‐ O ‐tetradecanoyl‐phorbol‐13‐acetate (TPA) exhibited mutations in Ha‐ ras and trisomy of chromosome 7. Carcinomas induced with multiple DMBA treatments had a lower frequency of alterations on chromosome 7 (50%), but only in tumors with Ha‐ ras mutations, and had a much wider spectrum of alterations, including trisomy, mitotic recombination, deletion, and gene duplication. Carcinomas induced with multiple N ‐methyl‐ N ‐nitro‐ N ‐nitrosoguanidine treatments only rarely exhibited alterations on chromosome 7 (8%), even if they contained mutant Ha‐ ras . More frequent numerical alterations of chromosome 11 were also seen in TPA‐promoted tumors (23%) than in tumors induced by multiple carcinogen treatments (8%). These results show that postinitiation events are nonrandom and fit a model in which promoting agents induce numerical chromosomal alterations but in which mutagens cause more directed mutational events. ©1994 Wiley‐Liss, Inc.